Biomedical subjects

S Lai

Publications and source records attributed to S Lai.

At least 19 recordsLinked to original sources

PubMed2007

Receptor-mediated internalization of chelator-PNA-peptide hybridization probes for radioimaging or magnetic resonance imaging of oncogene mRNAs in tumours.

Early external detection of cancer gene activity might enable early treatment of cancer and might reduce cancer mortality. We hypothesized that oncogene mRNA overexpressed at thousands of copies per malignant cell in a zone of transformed cells could be imaged externally by scintigraphic imaging, PET (positron emission tomography) or MRI (magnetic resonance imaging) with PNA (peptide nucleic acid) hybridization probes that include chelators for metal cations and a cyclized peptide analogue of IGF-1 (insulin-like growth factor 1), D(Cys-Ser-Lys-Cys), to mediate internalization by IGF1R (IGF-1 receptor) overexpressed on cancer cells. We observed that human MCF7 breast cancer cells that overexpress IGF1R efficiently internalized fluorescein-chelator-PNA-D(Cys-Ser-Lys-Cys) to the cytoplasm, but not with D(Cys-Ala-Ala-Cys). Scintigraphic imaging of MCF7 xenografts in immunocompromised mice revealed that CCND1 and MYC [(99m)Tc]chelator-PNA-D(Cys-Ser-Lys-Cys) probes yielded xenograft. PET imaging with [(64)Cu]chelator-PNA-D(Cys-Ser-Lys-Cys) yielded stronger signals. Scintigraphic imaging of human AsPC1 pancreas cancer xenografts with [(99m)Tc]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys) yielded strong xenograft signals. Stronger xenograft image intensities were obtained by PET imaging of [(64)Cu]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys). MRI required extension of chelator-polydiamidopropanoate dendrimers from the N-termini of the PNA probes to increase the number of contrast paramagnetic gadolinium (III) cations per probe. These results provide a basis for detection of oncogene activity in tissues from outside the body by hybridization with metal-chelator-PNA-peptides that are selectively internalized by cancer cells.

Animals↗

PubMed2006

Legionnaires' disease outbreak associated with a cruise liner, August 2003: epidemiological and microbiological findings.

Eight cases of Legionnaires' disease were identified among the 215 German passengers after a cruise to the Nordic Sea in August 2003. An unmatched case-control study was conducted to identify risk factors and the source of infection. In total, eight passengers fulfilled the case definition, one of these died. Forty-two passengers served as controls. The attack rate was 4%. The mean age was 60 years for cases and 62 years for controls. Prolonged exposure to the spa pool seemed to be a risk factor of infection (OR 4.85, P=0.09). Legionella pneumophila serogroup 1, monoclonal antibody (mAb) subgroup 'Knoxville' was isolated from clinical and environmental samples. DNA sequence-based typing revealed that these isolates were indistinguishable from each other. The investigation showed the importance of an interdisciplinary approach of microbiology and epidemiology as not all sites on the ship that tested positive for L. pneumophila actually posed a relevant risk for the passengers.

Adult↗

PubMed2006

Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada.

Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae were detected in patients admitted to Vancouver hospitals. Injection drug use, diabetes mellitus, skin colonization/infection with C. diphtheriae, and homelessness all appeared to be related to the development of bacteremia with the organism. Ribotyping of isolates recovered from blood culture revealed a predominant ribotype pattern that has not previously been reported in North America.

Adult↗

PubMed2006

Culture of Helicobacter pylori from domestic water samples--the impact of strain variation on growth on solid and in liquid media.

Helicobacter pylori is an important global human pathogen and there is growing evidence from PCR assays that contaminated drinking water might be a possible source of infection in some circumstances. There are no validated protocols for direct isolation but various culture media have been developed for possible environmental sampling. Our aim here was to investigate how inter-strain variation might affect the interpretation of results with such media. Two laboratory adapted reference strains and four recent clinical isolates were tested on four solid media and in ten liquid media. Considerable variation was found between strains in their ability to recover on the different media after stress exposure (suspension in sterile tap water). Generally, clinical isolates were less robust than the laboratory-adapted strains and, overall, the former required longer recovery times. Our findings highlighted the importance of using a range of isolates for evaluations, as examination of laboratory-adapted strains alone did not provide an accurate representation of the utility of media that may be used to recover H. pylori from water.

Culture Media↗

PubMed2005

Identification of a new allele, HLA-DRB11366.

High-resolution polymerase chain reaction sequence-specific primer typing of the human leucocyte antigen (HLA)-DRB1 gene of an Italian patient candidate for bone marrow transplantation revealed a new allelic variant of HLA-DRB1*13. The sequence was named DRB1*1366, and comparison with previously described DRB1 alleles demonstrated the two closely related sequences were HLA-DRB1*1330 and HLA-DRB1*130302.

Alleles↗

PubMed2004

Pleomorphic adenoma with extensive necrosis: report of two cases.

Pleomorphic adenoma (PA) is the most common neoplasm for both the major and minor salivary glands. While PA is occasionally associated with cystic change or hemorrhage necrosis, spontaneous infarction appears to be very uncommon. We report two unusual cases of extensive necrosis of PA; one occurred in the palate with the necrotic tumor mass slipping into the oral cavity. This phenomenon, possibly associated with incision biopsy, has never been described previously. A second case, arising in the parotid with spontaneous tumor necrosis, poses some dilemma in differential diagnosis.

Adenoma, Pleomorphic↗

PubMed2004

Detection of Helicobacter pylori by PCR but not culture in water and biofilm samples from drinking water distribution systems in England.

AIMS: To investigate treated water distribution systems in England as a source of Helicobacter pylori. METHODS AND RESULTS: Water and biofilms were obtained from 11 domestic and seven educational properties and from hydrants, reservoirs and water meters supplied by three water utilities. Samples were cultured on nonselective and antibiotic containing media combined with immunomagnetic separation concentration. Viable helicobacters were not detected in any of the 151 samples but Helicobacter-specific PCR assays detected DNA in 26% of samples from domestic properties, schools and hydrants with the highest frequency in biofilms (42%). Direct sequencing of six selected amplicons confirmed >95% sequence homology to H. pylori. CONCLUSIONS: While viable helicobacters were not isolated, evidence was obtained for the presence of Helicobacter DNA, including that of H. pylori. Biofilms on surfaces within water distribution systems may act either as sites for the passive accumulation of helicobacters or as potentially important reservoirs of infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings strengthen evidence that H. pylori may be transmitted through drinking water. However, there is currently no evidence that viable cells can survive the disinfection levels used in UK mains supplies and the health risk from this source remains unclear.

Base Sequence↗

PubMed2004

A psoriasis vulgaris protective gene maps close to the HLA-C locus on the EH18.2-extended haplotype.

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.

Adolescent↗

PubMed2004

A new germline RET mutation apparently devoid of transforming activity serendipitously discovered in a patient with atrophic autoimmune thyroiditis and primary ovarian failure.

Gain-of-function RET mutations are responsible for multiple endocrine neoplasia syndromes (MEN) 2A and 2B and familial medullary thyroid carcinoma (FMTC), whereas loss-of-function mutations are found in Hirschsprung disease. We report a new RET point mutation [R694Q (CGG-->CAG)], serendipitously found in a 23-yr-old woman with hypothyroidism due to atrophic Hashimoto's thyroiditis and primary ovarian failure, without altered calcitonin secretion. Familial history and clinical and biochemical evaluation of first-degree relatives were negative for FMTC, MEN 2A and 2B, and Hirschsprung disease. Genetic analysis showed that the mutation was inherited from the mother, who was submitted 2 yr before to thyroidectomy for goitrous Hashimoto's thyroiditis. Histological revision and immunohistochemical studies documented normal C cell number and morphology. We cloned the mutation in an expression vector encoding a full-length RET protein. The construct was transiently expressed in 293T cells in parallel with a wild-type RET and a C634R MEN 2A-associated RET mutant. Proteins were harvested from transfected cells, and tyrosine phosphorylation levels were assayed. The mutation did not exert significant potentiating effects on RET kinase. A focus assay was also performed on NIH3T3 fibroblasts; the mutant did not exert significant transforming activity. In conclusion, a new RET mutation was found in two subjects without any evidence of MEN and FMTC. In keeping with clinical data, transfection studies confirmed lack of activating activity. This serendipitous discovery, apparently devoid of oncogenic potential, underscores the problems that may be encountered in genomic studies on RET.

Adult↗

PubMed2003

Elevated C-reactive protein levels are associated with endothelial dysfunction in chronic cocaine users.

OBJECTIVE: To examine the relationship of the serum C-reactive protein (CRP) and endothelial function and their associations with coronary artery calcification, lipid profile and cardiac changes. METHODS: The analyses for serum lipids and CRP, echocardiography, spiral computed tomography scans and endothelial function assay were performed in 53 participants with a history of chronic cocaine use. RESULTS: There were no statistically significant differences in demographic characteristics and drug use between CRP normal (<1.9 mg/l) and abnormal groups. The brachial artery diameter percentage changes in the third scan (immediately after deflation of cuff) and the fourth scan (90 s after deflation of cuff) were significantly associated with the CRP levels (the third: beta=-0.054, S.E.=0.027; P=0.028; the fourth: beta=-0.065, S.E.=0.026; P=0.016). The multiple regression models showed that CRP was the only significant predictor of artery diameter changes (%) in these two scans. The CRP abnormal group had more coronary artery calcification (calcium scores >5, 16.7 vs. 0%; P=0.036) and more cardiac diastolic dysfunction expressed as deceleration time >240 ms (16.7 vs. 0%; P=0.036). CONCLUSIONS: Elevated serum CRP levels are associated with endothelial dysfunction, coronary artery calcification and cardiac diastolic dysfunction in chronic cocaine users.

Adult↗

PubMed2003

Suprarenal artery stenosis may be mistaken for renal artery stenosis in Doppler studies.

There are several limitations in using colour-flow-Doppler (CFD) to diagnose renal artery stenosis. This report describes a case of "false positive" stenosis of the renal artery diagnosed using CFD. A patient affected by arterial hypertension and with a suspected stenosis of the renal artery was examined using CFD. However, the patient was in fact suffering from suprarenal artery stenosis.

Aged↗

PubMed2003

Atherosclerotic ischemic renal disease.

AIM: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; its prevalence is inferred from autopsy or retrospective arteriographic studies. Screening investigation for ischemic nephropathy on large cohorts, based on non invasive diagnostic techniques, have not so far been published. This study has been conducted on 269 subjects over 50 with hypertension and/or chronic renal failure, unrelated to other known causes of renal disease. METHODS: All 269 patients were studied either by color-flow duplex sonography (n=238) or by renal scintigraphy (n=224), and 199 of the 269 patients were evaluated using both of these techniques. Forty patients, found to have renal artery stenosis, were subjected to 3D-contrast enhancement magnetic resonance angiography (MRA) and/or digital selective angiography (DSA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or DSA). RESULTS: Color-duplex sonography, carried out in 238 patients, revealed 49 cases of renal artery stenosis. MR or DSA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography was 91.7% sensitive and 90.9% specific, with positive predictive value of 94.2% and negative predictive value of 86.9%. Specificity and sensitivity of renal scintigraphy, carried out in 224 patients, was significantly lower. Patients with renal artery stenosis showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in the extent of proteinuria between the two groups. Renal artery stenosis, based on color-duplex sonography studies, was present in 11% of patients in the age group 50-59, 18% in the 60-69 and 23% at age 70 and above. CONCLUSION: A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by renal artery stenosis and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.

Aged↗

PubMed2002

New HLA-A11 allele, A1112, identified by sequence-based typing.

In this report, we describe the identification of HLA-A*1112, a novel HLA-A*11 allele found in two Italian families. The new allele was detected during routine HLA typing by a polymerase chain reaction sequence-specific primer and was confirmed by high-resolution sequencing-based typing. The nucleotide sequences of HLA-A*1112 exons 2 and 3 are identical to HLA-A*11011 except for a single nucleotide substitution in codon 90 (GAC-->GCC).

Alleles↗

PubMed2002

Could an echo contrast agent be helpful in identifying renal artery stenosis?

BACKGROUND: Diagnosis of renal artery stenosis using echo color-Doppler is subjected to several limitations. The aim of this study was to examine if the routine use of a contrast agent could be helpful in identifying renal artery stenosis (RAS). METHODS: We analysed 35 patients affected by RAS using an echo color-Doppler coupled with a contrast agent. All patients presented arterial hypertension, with a good drugs control, and mean serum creatinine of 1.8 mg/dL. All patients previously underwent angiography. RAS was at the origin of the artery in 27 patients, at the intermediate tract in 8. All patients had already been submitted to a basal echo color-Doppler. RESULTS: The contrast agent determined a significant increase in the average colour signal in all the subjects, and a better evaluation of the spectral waveforms, if compared to the basal examination. CONCLUSIONS: The results obtained showed that the contrast agent doesn't improve the diagnosis of RAS, especially in vascular origin stenosis, while it shows a real advantage in the intermediate or distal stenosis which are better visualized.

Adolescent↗

PubMed2002

Report on the Sixth International Meeting of the European Laboratory Working Group on Diphtheria, Brussels, Belgium.

In addition to the Eastern European resurgence of diphtheria during the last decade, there has also been an emergence of infections caused by non-toxigenic Corynebacterium diphtheriae and non-toxigenic, toxin gene bearing C. diphtheriae. Given that these strains may manifest as symptomatic infections of differing degrees of severity, their clinical and epidemiological significance need to be assessed. The persistence of toxigenic and non-toxigenic C. diphtheriae in circulation, together with genotypic and biotype variability means that innovative measures to vaccinate populations are pertinent. The most effective method of protecting the currently most vulnerable population group (adults) is to implement a booster dose of vaccine amongst the adult populations. Furthermore, in combination with an efficient surveillance system, effective antibiotic prophylaxis and an up-to-date vaccination programme, serological studies needs to be maintained to monitor the immunity status of the population.

Adult↗

PubMed2001

Tandem chain extension-aldol reaction: syn selectivity with a zinc enolate.

A tandem chain extension-aldol reaction was developed in which beta-keto esters are transformed to alpha-substituted-gamma-keto esters in an efficient zinc-mediated, one-pot reaction. The diastereoselectivity of the reaction ranged from good to excellent with syn stereochemistry observed for beta-keto ester and amide substrates and anti-stereochemistry observed for a beta-keto imide. [reaction: see text]

Aldehydes↗

PubMed2001

Sexual and drug risk-related behaviours after initiating highly active antiretroviral therapy among injection drug users.

OBJECTIVE: To assess whether initiation of highly active antiretroviral therapy (HAART) is associated with a subsequent resumption of sexual and drug use risk behaviors. METHODS: Within an ongoing prospective study of HIV-seropositive injection drug users (IDUs), a subsample with at least one CD4 cell count < 500 x 106 cells/l after 1996 (when HAART became available) and three consecutive visits were selected for analysis. Patients underwent semi-annual interviews for risk behaviors and reports of medication use. Data from visits immediately prior to and following initiation of HAART for the treated group, and from consecutive visits for the eligible but untreated group were compared using linear growth curve analysis. RESULTS: Of 316 eligible HIV-seropositive IDUs, 133 reported HAART use during the study period; 95% were African American, 76% were male, and median age at enrollment was 34 years. The proportion who reported any sexual activity increased over time from 55 to 61% for the HAART-treated group, but decreased from 67 to 63% in the untreated group (P = 0.03); the respective values for unprotected sex were 18 versus 20% and 36 versus 28% (P = 0.06). In both treated and untreated groups, the proportion injecting drugs declined (P = 0.04), whereas the proportion reporting needle sharing decreased marginally (P = 0.11). However, trends in use of shooting galleries between the groups differed (P = 0.04) increasing slightly from 2.3 to 3% in the treated group while decreasing from 12 to 5% in the untreated group. CONCLUSION: In persons treated with HAART, self-report of high-risk behaviors remained stable or showed some increase. Persons initiating HAART should be counselled to refrain from high-risk behaviors.

Adult↗

PubMed2001

Development of a fully integrated analysis system for ions based on ion-selective optodes and centrifugal microfluidics.

A fully integrated, miniaturized analysis system for ions based on a centrifugal microfluidics platform and ion-selective optode membranes is described. The microfluidic architecture is composed of channels, five solution reservoirs, a measuring chamber, and a waste reservoir manufactured onto a disk-shaped substrate of poly(methyl methacrylate). Ion-selective optode membranes, composed of plasticized poly(vinyl chloride) impregnated with an ionophore, a proton chromoionophore, and a lipophilic anionic additive, were cast, with a spin-on device, onto a support layer and then immobilized on the disk. Fluid propulsion is achieved by the centrifugal force that results from spinning the disk, while a system of valves is built onto the disk to control flow. These valves operate based on fluid properties and fluid/substrate interactions and are controlled by the angular frequency of rotation. With this system, we have been able to deliver calibrant solutions, washing buffers, or "test" solutions to the measuring chamber where the optode membrane is located. An analysis system based on a potassium-selective optode has been characterized. Results indicate that optodes immobilized on the platform demonstrate theoretical responses in an absorbance mode of measurement. Samples of unknown concentration can be quantified to within 3% error by fitting the response function for a given optode membrane using an acid (for measuring the signal for a fully protonated chromoionophore), a base (for fully deprotonated chromoionophore), and two standard solutions. Further, the ability to measure ion concentrations by employing one standard solution in conjunction with acid and base and with two standards alone were studied to delineate whether the current architecture could be simplified. Finally, the efficacy of incorporating washing steps into the calibration protocol was investigated.

Calibration↗