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Biomedical subjects

M Lai

Publications and source records attributed to M Lai.

At least 37 records · Page 2Linked to original sources
PubMed2002

The number of markers of pancreatic autoimmunity is proportional to the risk for type 1 diabetes mellitus in Italian and English patients with organ-specific autoimmune diseases.

An 11-year prospective study was carried out in 226 patients with organ-specific autoimmune disease (OSAD) coming from northern Italy and southern England. Patients were investigated for diabetes-related autoantibodies (ICAs, GADAbs, and IA2Abs) in order to evaluate the best immunological combination in predicting type 1 DM. One hundred twenty-eight patients were ICA positive (77 Italian and 51 English), and 98 were ICA negative. ICAs were detected by immunofluorescence technique on human pancreas, whereas GADAbs and IA2Abs were found by immunoprecipitation assay. During follow-up, 33 of 128 (25.8%) ICA(+) (26% of Italian and 25.5% of English) and 2 of 98 (2%) ICA(-) patients developed type 1 DM (17 with acute-onset, and 18 with non-acute-onset disease). Among ICA(+) patients, three subgroups were considered: ICA(+) alone; ICA and GADAb(+); ICA, GADAb, and IA2Ab(+). Patients who were only ICA(+) had a predictive value for type 1 DM of 4.7%, with an annual incidence of 0.7%, and a cumulative risk of 6%. ICA and GADAb(+) patients had a predictive value of 17.5%, with an annual incidence of 2%, and a cumulative risk of 20%. ICA, GADAb, and IA2Ab(+) patients had a predictive value of 72, with an annual incidence of 13%, and a cumulative risk of 87%. Patients having three immunological markers revealed a prevalence increased in HLA-DR3 and/or -DR4, but reduced in HLA-DR2 haplotypes. The risk for type 1 DM increased proportionally with the number of diabetes-related antibodies, which were also related to the presence of genetic markers of disease susceptibility.

Adult↗
PubMed2002

11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons.

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.

Adrenal Glands↗
PubMed2002

Clinically significant autoimmune hemolytic anemia with a negative direct antiglobulin test by routine tube test and positive by column agglutination method.

In two to five percent of cases of autoimmune hemolytic anemia (AIHA),the patient's RBCs are negative in the direct antiglobulin test (DAT). We describe a patient with AIHA with a negative DAT when tested by the traditional tube test but with a strongly positive one when tested by column agglutination. When the DAT was repeated by tube test using 4 degrees Celsius saline washes, it became positive. This phenomenon has been observed when low-affinity antibodies are involved in AIHA. The patient's history and serologic findings are detailed in this report.

Journal Article↗
PubMed2001

Overexpression of HER-2/neu enhances the sensitivity of human bladder cancer cells to urinary isoflavones.

Soybean foods have been suggested to be practical chemopreventives for human urinary tract cancers. Recently, we demonstrated that the co-operative action of isoflavones results in an increased dose-dependent growth inhibition and apoptosis than any single isoflavone compound. This study aimed to examine the potential of HER-2/neu as a biological target for soy isoflavones. The sensitivity of the bladder cancer cell lines (n=7) to the isoflavones was inversely related to the amount of HER-2/neu expressed. By using HER-2/neu transfection experiments, all three stable transfectants showed a significant growth inhibition by the isoflavone mixture at concentrations attainable in normal adult urine. An increased inhibition of tyrosine phosphorylation of proteins immunoprecipitated by HER-2/Neu was observed in the neu-transfectants compared with controls. The results of this study suggest that HER-2/neu may be a practical biochemical target for urinary isoflavones in vivo.

Antineoplastic Agents, Phytogenic↗
PubMed2001

A genome screen for multiple sclerosis in Sardinian multiplex families.

The prevalence of multiple sclerosis in Sardinia is significantly higher than in neighbouring Mediterranean countries, suggesting that the isolated growth of the population has concentrated genetic factors which increase susceptibility to the disease. The distinct HLA association of multiple sclerosis in Sardinia supports this interpretation. We have performed a whole genome screen for linkage in 49 Sardinian multiplex families using 327 markers. Non parametric linkage analysis of these data reveal suggestive linkage in the region of Chr 1q31, Chr 10q23 and Chr 11p15.

Genetic Linkage↗
PubMed2001

Down-regulation of inducible nitric-oxide synthase (NOS-2) during parasite-induced gut inflammation: a path to identify a selective NOS-2 inhibitor.

Nitric oxide (NO) possesses potent anti-inflammatory properties; however, an over-production of NO will promote inflammation and induce cell and tissue dysfunction. Thus, the ability to precisely regulate NO production could prove beneficial in controlling damage. In this study, advantage was taken of the well characterized inflammatory response caused by an intestinal parasite, Trichinella spiralis, to study the relationship between intestinal inflammation and the regulation of nitric oxide synthase-type 2 (NOS-2) expression. Our study revealed that a specific gut inflammatory reaction results in inhibition of NOS-2 expression. Characteristics of this inhibition are: 1) local jejunal inflammation induced by T. spiralis systemically inhibits NOS-2 gene transcription, protein expression, and enzyme activity; 2) the inhibition blunts endotoxin-stimulated NOS-2 expression; 3) the inhibition does not extend to the expression of other isoforms of NOS, to paxillin, a housekeeper protein, or to cyclooxygenase-2, another protein induced by proinflammatory cytokines; 4) the inhibition is unlikely related to the formation of specific anti-parasite antibodies; and 5) the inhibition may involve substances other than stress-induced corticosteroids. Elucidation of such potent endogenous NOS-2 down-regulatory mechanisms could lead to the development of new strategies for the therapy of inflammatory conditions characterized by the overproduction of NO.

Animals↗
PubMed2001

Mutagen sensitivity and p53 expression in colorectal cancer in China.

OBJECTIVE: This study was designed to investigate DNA damage and/or repair capability, non-random chromatid breakage, and p53 expression in patients with colorectal cancer. METHODS: The bleomycin sensitivity assay was used in a case-control study to compare the DNA damage repair system between colorectal cancer patients and controls. G-banding was used to search for non-random chromatid breaks. Immunocytochemistry was used to investigate p53 expression in tumour tissues and adjacent normal tissues. RESULTS: It was found that cases typically had a higher number of chromosome breaks than controls (0.84 v 0.69 breaks/cell, p<0.01). After correction by sex and age, the difference was still significant (F=4.38, p<0.05). The correlation coefficient between mutagen sensitivity and age was 0.31(p<0.05) in controls and 0.18 (p>0.05) in cases. The ratio of odds ratios among bleomycin resistant, sensitive, and hypersensitive classes was 1:2.31:3.85. Overexpression of p53 was detected in 25 of 47 tumour tissues independent of tumour stage. Cases who had a family history of cancer were susceptible to the p53 aberration (p<0.05). Chromosomes 1p, 5q, and 14q were susceptible to breakage in patients with colorectal cancer. CONCLUSION: Patients with colorectal cancer show increased bleomycin induced chromatid breaks and may have minor DNA repair deficiencies. p53 aberration is an early event in the development of colorectal cancer, but no definite correlation is found between p53 overexpression and mutagen sensitivity.

Adolescent↗
PubMed2001

MAPD--an objective way to select mAs for paediatric brain CT.

CT is an advanced imaging modality, but the imaging parameters are normally selected subjectively. For standard head examinations, most of the parameters used are consistent amongst different centres, with the exception of large variations in the selection of the tube current-exposure time product (mAs). As a result, CT images may contain unacceptable levels of noise, or the patient may receive excessive radiation. In this study, the maximum anteroposterior diameter (MAPD) was shown to be a good criterion for mAs selection, and could be measured in a pilot view. 200 paediatric brain CT studies were randomly selected to determine the MAPD at the mid brain level. With knowledge of MAPD distribution, a phantom study was performed to determine the relationship between MAPD and the mAs required for consistent and acceptable image noise. It was found that the required mAs increased linearly with MAPD. Assuming the manufacturer's recommended value is "appropriate" for the average MAPD, the appropriate mAs value could be estimated. Using this method, appropriate mAs values were calculated retrospectively for a group of 240 randomly selected paediatric brain CT studies and compared with the actual mAs subjectively determined by the radiographer. Although their average values were similar, the difference between the calculated and actual values deviated markedly in some cases. When the actual mAs was smaller than the calculated value, higher image noise was observed. However, reduction of image noise was barely observed when the applied mAs was larger than the calculated value. Thus, this method is more objective and appropriate for determination of the mAs value for paediatric brain CT than the traditional subjective method.

Brain↗
PubMed2001

The cost of palliative care for hepatocellular carcinoma in Hong Kong.

BACKGROUND: Hepatocellular carcinoma (HCC) is endemic in parts of Asia and Africa and most patients are not suitable for treatment with a curative approach. Little is known about the cost of palliative care for HCC. OBJECTIVE: To determine: (i) patient-specific costs of palliative care of HCC; and (ii) individual factors that drive patient-specific costs and to develop a model of cost per case under alternative circumstances. METHODS: 204 patients with inoperable HCC were prospectively tracked from first hospitalisation until death for health service utilisation. A societal perspective of cost was taken, including costs of formal and informal services incurred by payers, caregivers and patients. Observational data from a large Hong Kong cancer care programme were used. A regression analysis was performed using formal costs only, with the cost per observed day as the dependent variable. RESULTS: The median survival was 95 days and the mean observation period was 153 days. The mean value per person for formal healthcare cost was 30 983 Hong Kong dollars [$HK] ($US3872, 1998 values). The distribution of cost values were positively skewed. The regression analysis showed that age, days of observation and survival were negatively related to cost per observed day, and the Child-Pugh grading of severity of liver cirrhosis was positively related to cost per observed day. A sensitivity analysis based on the regression equation indicated that nonsurvivorship doubles the cost per case, increased severity as measured by the Child-Pugh Index adds about 50% to the cost, and chemotherapy increases cost 2-fold. CONCLUSIONS: The relatively modest average cost per patient with HCC in Hong Kong reflects the short median survival and subsequently the limited use of inpatient care and chemotherapy.

Aged↗
PubMed2001

Healthcare architecture in metamorphosis--observations in Hong Kong's heuristic experience.

Healthcare Architecture in Hong Kong is in an on-going process of metamorphosis in response to the social, economical and technological developments in the territory. In the process of transformation, universal problems like obsolescence, growth and expansion, and advances in science and technology as well as problems unique to Hong Kong like population growth, scarcity in land supply and high density development all call for special solutions. With the turn of the century, new forces of change have also begun to take shape, and in anticipation of the hyper-turbulent changes ahead, we need to shift our paradigm to allow revolutionary new perspectives and innovate, shape and create the future healing space which is sustainable, adaptable, flexible and humane.

Architecture↗
PubMed2000

Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity.

We have characterized a series of nonsteroidal progesterone receptor ligands, the tetrahydropyridazines. Compounds in this series, exemplified by RWJ 26819, demonstrate high affinity and unprecedented specificity for the progesterone receptor relative to other steroid hormone receptors. Like steroidal progestins, RWJ 26819 induces binding of the receptor to a progesterone response element in vitro, and stimulates gene expression in and proliferation of T47D human breast cancer cells. When administered to rabbits orally or subcutaneously, the compound induces histological changes in the uterine lining comparable to those induced by levonorgestrel. It also inhibits ovulation in monkeys. Though less potent in cells and in animal models than would be predicted from binding affinity alone, their enhanced selectivity suggests that they could be effectively used in a clinical setting. Most of the tetrahydropyridazines synthesized are progestin agonists or mixed agonists and antagonists in vitro; however, one compound with antagonist activity in the rabbit uterine transformation assay has been identified.

Alkaline Phosphatase↗
PubMed2000

Heterogeneous nuclear ribonucleoproteins as regulators of gene expression through interactions with the human thymidine kinase promoter.

In search for nuclear proteins that interact with the human thymidine kinase (htk) promoter, we discovered that p37AUF, a hnRNP C-like protein, and hnRNP A1, both members of the heterogeneous ribonucleoprotein family, can bind with high affinity to an ATTT sequence motif contained within the cell cycle regulatory unit (CCRU). We report here that over-expression of p37AUF stimulates gene expression mediated by the htk promoter in a promoter-sequence specific manner, whereas hnRNP A1 suppresses it. Both recombinant p37AUF and hnRNP A1 can bind the htk CCRU, suggesting that their binding to the DNA target does not require additional cellular components. We further discovered that hnRNP K is a potent suppressor of htk mediated gene activity. However, its mechanism of action is mediated through protein-protein interaction, since hnRNP K itself cannot bind the htk CCRU but can competitively inhibit the binding of other hnRNPs. The binding site for the hnRNPs on the htk CCRU is not required for S-phase induction of the htk promoter. However, in stable but not transient transfectants, the mutation of the hnRNP binding site results in 5- to 10-fold reduction of htk mediated gene activity in synchronized and exponentially growing cells. Collectively, these findings support emerging evidence that hnRNPs, in addition to their traditional role in RNA biogenesis, could be regulators of gene expression through direct DNA binding or interaction with other proteins.

Amino Acid Sequence↗
PubMed2000

Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy.

BACKGROUND: Mental retardation is a clinical feature of Duchenne dystrophy (DD) and affects about one-third of patients. No clear association has been found between DNA mutations, protein expression, and IQ scores, although distal deletions in the dystrophin gene have been reported in association with intellectual impairment. A role for the brain distal dystrophin isoform Dp140 was suggested. OBJECTIVE: To explore the possible association between cognitive impairment and DNA macrodeletions in the distal part of the gene, including Dp140 gene region. METHODS: Sixty-six patients with DD received general intelligence assessment by Wechsler Intelligence Scales measuring full, verbal, and performance IQ. PCR analysis was performed to detect deletions in the dystrophin gene, and the Dp140 regulatory region was analyzed in a subgroup of 12 patients. Statistical analysis was performed by nonparametric Wilcoxon rank signed and rank sum tests. RESULTS: Comparison of neuropsychological and genetic data revealed an association between distal macrodeletions and cognitive impairment (p < 0.001). Comparing deletions involving the Dp140 gene region with deletions presumably not altering Dp140 expression resulted in even greater significance. CONCLUSIONS: These data suggest that in DD, distal dystrophin deletions are associated with intellectual impairment. This study highlights a possible role for the brain distal isoform Dp140 in normal cognitive development.

Adolescent↗
PubMed2000

Reduced expression of insulin-like growth factor 1 messenger RNA in the hippocampus of aged rats.

Adult neurones remain dependent on neurotrophic factors such as insulin-like growth factor 1 (IGF-1) to sustain neuronal viability by maintaining cell phenotype, supporting synaptic plasticity and providing neuroprotective and neuroregenerative mechanisms. A decline in the cellular expression of neurotrophic factors has been speculated to contribute to the age-related changes that occur in the brain, where the hippocampus appears particularly susceptible. Using in situ hybridisation, we have made a detailed comparison of the expression of IGF-1 mRNA in the hippocampal formation between young (6 months) and aged (23 months) rats. IGF-1 mRNA expression was measured from cell populations containing only high density radioactive labelling (>20 grains/cell) to avoid ambiguity of signal. The amount of IGF-1 mRNA signal was significantly lower in cells of the alveus (P<0.05) and stratum lacunosum moleculare (P<0.01) of aged compared to young rats. These findings challenge reports that IGF-1 mRNA is unaltered in the ageing hippocampus and provide further evidence that changes in the IGF-1 system is a significant factor in the progressive age-related deterioration of normal neuronal function.

Aging↗
PubMed2000

ICAM-1 gene is not associated with multiple sclerosis in sardinian patients.

An increased amount of the intercellular adhesion molecule (ICAM) 1 molecule has been found in the blood of actively relapsing multiple sclerosis (MS) patients, but is unclear whether this enhanced expression is partially causative of the MS process, or whether it is merely an epiphenomenon of the inflammatory-immunological reaction. Using the transmission disequilibrium test (TDT), we studied exon 4 and exon 6 polymorphism of the ICAM-1 gene from 157 families with both parents, one affected and one healthy sib coming from Sardinia, an Italian island having a high incidence and prevalence of MS. TDT did not show variation in the expected 50:50 frequency in transmission in either healthy or affected sibs, using phenotypic or genotypic analysis. Moreover, independence from the predisposing HLA-DRB1-DQA1-DQB1 haplotype was confirmed by TDT analysis performed on patients stratified according to the presence or absence of the HLA-DRB1, DQA1, DQB1 Sardinian predisposing haplotypes. Our data suggest that the increased expression of the ICAM-1 molecule observed in both blood and periplaque microvessels may be considered a consequence of the inflammatory process rather than the result of a genetic variation.

Adult↗
PubMed2000

First operation anatomic success and other predictors of postoperative vision after complex retinal detachment repair with vitrectomy and silicone oil tamponade.

PURPOSE: To evaluate the role of first operation anatomic success compared with success after reoperation and preoperative characteristics in achieving ambulatory vision (>/=4/200) and good vision (>/=20/100) after repair of complex retinal detachment with vitrectomy and silicone oil tamponade. METHODS: A prospective, observational, multicenter study of patients who underwent vitrectomy with silicone oil for retinal detachments associated with cytomegalovirus necrotizing retinitis or a non-cytomegalovirus necrotizing retinitis etiology, including proliferative diabetic retinopathy, giant retinal tear, proliferative vitreoretinopathy, and ocular trauma. RESULTS: A higher rate of ambulatory vision was achieved in the first operation anatomic success cases, compared with the reoperation cases, for eyes with cytomegalovirus necrotizing retinitis (72% vs 50%, P < 0.01) and eyes without cytomegalovirus necrotizing retinitis (51% vs 38%, P = 0.04). For eyes with cytomegalovirus necrotizing retinitis, preoperative ambulatory vision (RR = 2.3, P < 0.0001) and reoperation (RR = 0.4, P = 0.05) were independent predictors of postoperative ambulatory vision. For eyes without cytomegalovirus necrotizing retinitis, preoperative ambulatory vision (RR = 4.0, p < 0.0001) and retinal detachment etiology (P = 0.02) were prognostic factors. Compared to eyes with trauma, eyes with giant retinal tear, proliferative vitreoretinopathy and proliferative diabetic retinopathy were 2.8 (P < 0.003), 2.2 (P = 0.01) and 1.6 (P = 0.17) times as likely to achieve postoperative ambulatory vision, respectively. Within the giant retinal tear group, a higher rate of ambulatory vision was achieved in the first operation anatomic success cases compared with the reoperation cases (66% vs 31%, P = 0.03). Although not statistically significant, similar outcomes occurred in the proliferative diabetic retinopathy (48% vs 25%) and proliferative vitreoretinopathy groups (54% vs 45%). Similar prognostic relationships were found for good visual acuity outcomes. CONCLUSIONS: First operation anatomic success, preoperative visual acuity, and giant retinal tear or proliferative vitreoretinopathy as the retinal detachment etiology are important factors that predict visual outcome.

Adult↗
PubMed2000

Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies.

Mental retardation is a clinical feature present in both Duchenne and Becker muscular dystrophy patients and its pathogenesis is still unknown. Dp140 is a dystrophin isoform with predominant expression during foetal brain development. Its promoter and first exon lie in the large intron between exon 44 and 45, a region that is commonly deleted in dystrophinopathic patients. We performed neuropsychological evaluation and genetic analysis of the Dp140 transcription unit on 12 Duchenne muscular dystrophy and 28 Becker muscular dystrophy patients carrying deletions in this critical region. Comparison of neuropsychological and molecular data showed that there is a statistically significant relationship between the loss of Dp140 transcription unit and mental retardation in Becker muscular dystrophy patients (P = 0.008). Such a correlation is not evident in Duchenne muscular dystrophy patients but only shows a trend towards significance (P = 0.063). It is worth noting that both Duchenne muscular dystrophy and Becker muscular dystrophy patients with normal intelligence do not show deletions in the Dp140 regulatory regions. In the light of these findings, we suggest that impairment of cognitive abilities in Duchenne muscular dystrophy and Becker muscular dystrophy patients might be related to a dysfunction of Dp140 brain isoform.

Adolescent↗