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Biomedical subjects

L Yip

Publications and source records attributed to L Yip.

At least 19 recordsLinked to original sources
PubMed2004

Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism.

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Adolescent↗
PubMed2001

Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal cells by microsatellite analysis.

Prompt detection of head and neck squamous cell carcinoma (HNSCC) is vital to successful patient management. In this feasibility study, we used microsatellite analysis to detect tumor-specific genetic alterations in exfoliated oral mucosal cell samples from patients with known cancer. Exfoliated mucosal cells in pretreatment oral rinse and swab samples were collected from 44 HNSCC patients and from 43 healthy control subjects (20 nonsmokers and 23 smokers). We tested a panel of 23 informative microsatellite markers to assay DNA from the matched lymphocyte, tumor (from cancer cases), and oral test samples. Loss of heterozygosity or microsatellite instability of at least one marker was detected in 38 (86%) of 44 primary tumors. Identical alterations were found in the saliva samples in 35 of these 38 cases (92% of those with markers; 79% overall) including 12 of 13 cases with small primaries [stage Tt or Tx (occult primary)] and 4 of 4 cases of patients that had undergone prior radiation. Microsatellite instability was detectable in the saliva in 24 (96%) of 25 cases in which it was present in the tumor, and loss of heterozygosity was identified in the test sample in 19 (61%) of 31 cases. No microsatellite alterations were detected in any of the samples from the healthy control subjects. This approach must now be refined and validated for the detection of clinically occult disease. Microsatellite analysis of oral samples may then become a valuable method for detecting and monitoring HNSCC.

Carcinoma, Squamous Cell↗
PubMed2001

Clinical audit on the incidence of inferior alveolar nerve dysfunction following mandibular sagittal split osteotomies at the Derby Royal Infirmary, England.

This retrospective clinical audit identified the incidence of inferior alveolar nerve dysfunction following mandibular sagittal split osteotomies for a period of 1 year at the Derby Royal Infirmary. The clinical notes of 50 consecutive patients treated with a bilateral sagittal split osteotomy over the last 5 years were used to collect information on the following: age, sex, type of mandibular movement (advancement or setback), recorded nerve damage during surgery, "good" or "bad" split, and the presence of nerve dysfunction at representative postoperative intervals, up to 1 year. One hundred procedures were essentially audited, as the surgery was carried out on both sides. The mean age of patients undergoing this procedure was 23 years. Thirty-four patients were female and 16 were male. Thirty-three patients underwent advancements and 17 underwent setbacks. The only nerve damage recorded was stretching; this occurred in 11 procedures. The incidence of nerve dysfunction recorded postoperatively was: 22% to 78% immediately, 29% to 61% after 1 week, 23% to 45% after 1 month, 8% to 34% after 3 months, 5% to 26% after 6 months, and 22% to 78% after 1 year. The findings from this clinical audit show that the incidence of inferior alveolar nerve dysfunction at the Derby Royal Infirmary is comparable to, if not less than, what was reported in previous studies. Hence, there is evidence of a reasonably high standard of care taken to prevent this damage, and no changes in the way the surgical procedure is carried out is indicated at present. However, this clinical audit did highlight the lack of documentation and standardization of postoperative assessment for nerve dysfunction. There may be a need for the introduction of a pro forma assessment system to the department.

Adult↗
PubMed2000

DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine.

The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure.

Adult↗
PubMed2000

Two distinct regions of loss on chromosome arm 4q in primary head and neck squamous cell carcinoma.

OBJECTIVE: To more clearly define the frequency and the regions of chromosome arm 4q loss in head and neck squamous cell carcinoma. DESIGN: A retrospective microsatellite analysis of DNA from previously microdissected primary tumor samples. SETTING: Academic medical center. PATIENTS AND METHODS: One hundred primary tumor samples from patients with head and neck squamous cell carcinoma were analyzed for loss of heterozygosity on the long arm of chromosome 4. The Kaplan-Meier method was used to estimate survival for 97 patients for whom clinical data were available. The Cox proportional hazards model was used to compare survival, and logistic regression was used to search for associations between clinical tumor characteristics and 4q status. RESULTS: Analysis of 33 polymorphic microsatellite markers identified 51 samples (51%) exhibiting loss of heterozygosity of 4q in at least 1 locus. Eighteen tumors revealed loss at all informative markers, indicating monosomy or complete deletion of 4q. Thirty-three tumors displayed partial loss of heterozygosity and delineated 2 minimal areas of loss at 4q2324 and 4q2829. Eleven tumors displayed loss solely at the 4q2324 region, 13 tumors displayed deletions confined to the 4q2829 region, and 9 tumors displayed selective loss at both regions. A separate analysis in a subset of 94 primary head and neck tumors was done to further delineate the minimal area of chromosomal loss at 4q2324. Analysis of 8 markers in this region allowed us to identify the smallest region of loss between markers D4S2986 and D4S1564 (a distance of 2 centimorgans). Review of the clinical records of 97 patients revealed no statistically significant association between 4q status and any clinical variable, including survival. CONCLUSION: These results confirm a high frequency of chromosome arm 4q loss in primary head and neck squamous cell carcinoma and might demarcate 2 novel putative suppressor loci involved in progression of this carcinoma.

Adult↗
PubMed2000

Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic.

Monomethylarsonous acid (MMA(III)) has been detected for the first time in the urine of some humans exposed to inorganic arsenic in their drinking water. Our experiments have dealt with subjects in Romania who have been exposed to 2.8, 29, 84, or 161 microg of As/L in their drinking water. In the latter two groups, MMA(III) was 11 and 7% of the urinary arsenic while the monomethylarsonic acid (MMA(V)) was 14 and 13%, respectively. Of our 58 subjects, 17% had MMA(III) in their urine. MMA(III) was not found in urine of any members of the group with the lowest level of As exposure. If the lowest-level As exposure group is excluded, 23% of our subjects had MMA(III) in their urine. Our results indicate that (a) future studies concerning urinary arsenic profiles of arsenic-exposed humans must determine MMA(III) concentrations, (b) previous studies of urinary profiles dealing with humans exposed to arsenic need to be re-examined and re-evaluated, and (c) since MMA(III) is more toxic than inorganic arsenite, a re-examination is needed of the two hypotheses which hold that methylation is a detoxication process for inorganic arsenite and that inorganic arsenite is the major cause of the toxicity and carcinogenicity of inorganic arsenic.

Adolescent↗
PubMed2000

Polyphenol oxidase from hybrid poplar. Cloning and expression in response to wounding and herbivory.

The inducible expression of polyphenol oxidase (PPO), a presumed antiherbivore enzyme, was examined in hybrid poplar (Populus trichocarpa x Populus deltoides). Following mechanical wounding simulating insect damage, PPO activity increased dramatically in wounded and unwounded leaves on wounded plants beginning at 24 and 48 h, respectively. A hybrid poplar PPO cDNA was isolated and its nucleotide sequence determined. On northern blots, PPO transcripts were detected within 8 h of wounding, and reached peak levels at 16 and 24 h in wounded and unwounded leaves, respectively. Methyl jasmonate spray and feeding by forest tent caterpillar also induced PPO expression. The induction of PPO was strongest in the youngest four leaves, which were generally avoided by caterpillars in free feeding experiments. This wound- and herbivore-induced expression of PPO in hybrid poplar supports the defensive role of this protein against insect pests.

Acetates↗
PubMed2000

Skin prick test reactivity to recombinant latex allergens.

BACKGROUND: Allergy to latex has become a serious and increasingly common health problem, particularly for healthcare workers and patients who undergo frequent surgical procedures. Testing for latex allergy currently involves in vitro tests and skin prick testing using crude preparations of natural rubber latex (NRL). To date, 10 latex proteins have received designation as allergens (Hev b 1 to Hev b 10) and, except for Hev b 4, have been cloned as recombinant proteins. Our aim was to compare the skin prick test (SPT) reactivity of six recombinant latex allergens with SPT reactivity to natural rubber latex proteins in known latex-allergic individuals. METHODS: Six recombinant proteins were expressed in Escherichia coli, and tested as the intact fusion proteins (Hev b 2, 5, 6, 8) or as purified proteins (Hev b 3 and 7). SPT with the six recombinant latex allergens was performed using 10-fold serial dilutions on 31 latex-allergic subjects to determine the level of reactivity to each recombinant allergen. Latex-specific IgE was determined using the AlaSTAT assay. RESULTS: All six recombinant allergens were reactive by SPT in at least 1 latex-allergic patient but not in any of the control patients. The frequency of sensitization to the various recombinant allergens was similar to previous studies using the native proteins isolated from NRL. The minimal level of protein for a positive skin test was 70 pg/ml for NRL and 1 ng/ml for one recombinant allergen (Hev b 7). In our patients, the use of a combination of recombinant latex allergens Hev b 5, 6 and 7 diagnosed latex allergy with 93% sensitivity and 100% specificity. CONCLUSION: Recombinant latex allergens are clinically reactive, can be produced in a standardized manner, and could potentially provide safe, sensitive and specific reagents for the diagnosis of latex allergy.

Adult↗
PubMed1999

Chromosome 9p21 loss and p16 inactivation in primary sclerosing cholangitis-associated cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is a frequent complication of primary sclerosing cholangitis and is a leading cause of mortality in patients with this disease. The tumor suppressor gene p16 is commonly inactivated in many neoplasms; however, the role of p16 in the pathogenesis of cholangiocarcinoma is unclear. Therefore, we examined the role of p16 inactivation in the pathogenesis of cholangiocarcinoma associated with primary sclerosing cholangitis. MATERIALS AND METHODS: Paraffin-embedded sections from 10 patients who developed cholangiocarcinoma in the setting of primary sclerosing cholangitis were examined. Chromosomal loss at 9p21 was determined using microsatellite analysis. Methylation of a CpG island in the promoter region of the p16 gene was determined using methylation-specific polymerase chain reaction. p16 inactivation was also determined using immunohistochemistry. RESULTS: Allelic loss at chromosome 9p21 was present in 9 of 10 tumors (90%). Methylation of the p16 promoter was present in 2 of the 8 tumors examined (25%). Four of seven tumors (57%) analyzed by immunohistochemistry demonstrated an absence of p16 nuclear staining. CONCLUSIONS: Loss of chromosome 9p21 and inactivation of the p16 tumor suppressor gene are common events in primary sclerosing cholangitis-associated cholangiocarcinoma and may play a role in the high incidence of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Adult↗
PubMed1999

Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin.

BACKGROUND: Unknown primary head and neck squamous cell carcinoma (HNSCC) presents as a cervical lymph node metastasis without identification of the primary tumor, despite thorough diagnostic work-up that includes physical examination, computed tomography, esophagoscopy, laryngoscopy, bronchoscopy, and multiple surveillance biopsies. We investigated whether the site of origin of the primary tumor could be localized in the upper aerodigestive tract mucosa by detection of genetic alterations identical to those found in metastatic lesions. METHODS: Microsatellite analysis was performed on metastatic tumors obtained from 18 patients with unknown primary HNSCC. Histologically benign surveillance biopsy specimens were also analyzed. Patients were followed up to 13 years with continuing surveillance for primary mucosal tumors. Most patients were treated with neck dissection followed by radiation therapy to the affected neck and ipsilateral Waldeyer's ring. RESULTS: In 10 (55%) of the 18 patients, at least one histopathologically benign mucosal biopsy specimen from defined anatomic sites (i.e., most likely sites for an occult primary tumor) demonstrated a pattern of genetic alterations identical to that present in cervical lymph node metastases. One patient harboring genetic alterations in the base of the tongue and two patients harboring genetic alterations in a tonsillar fossa subsequently developed HNSCC in the identical or adjacent mucosal region; all three of the primary head and neck mucosal tumors that eventually appeared between 1 and 13 years later in these patients had genetic changes identical to those in the benign mucosal biopsy specimens and in the metastatic lymph nodes. CONCLUSIONS: These data support the hypothesis that histopathologically benign mucosa of the upper aerodigestive tract may harbor foci of clonal, preneoplastic cells that are genetically related to metastatic HNSCC and that such mucosal sites are the sites of origin of unknown primary HNSCC. Microsatellite analysis may represent a clinically useful tool for determining such sites.

Carcinoma, Squamous Cell↗
PubMed1998

Prosystemin from potato, black nightshade, and bell pepper: primary structure and biological activity of predicted systemin polypeptides.

Prosystemin is the precursor protein of the 18 amino acid wound signal systemin which activates systemic defense in tomato leaves against insect herbivores (McGurl B, Pearce G, Orozco-Cardenas M, Ryan CA, Science 255 (1992) 1570-1573). Here, we report the isolation of cDNA sequences encoding prosystemin from potato (Solanum tuberosum), black nightshade (S. nigrum), and bell pepper (Capsicum annuum), all members of the Solanaceae family, using reverse-transcription polymerase chain reaction (RT-PCR). Pairwise comparisons of the predicted prosystemin proteins from the three species with tomato prosystemin and among each other indicated sequence identities ranging from 73% to 88%. The deduced systemin polypeptides were synthesized and tested for their capacities to induce the synthesis of the defensive proteinase inhibitors in tomato leaves. Potato and pepper systemins were approximately as active as tomato systemin, whereas nightshade systemin was ten-fold less active. The accumulation of proteinase inhibitor mRNA transcripts could be induced in each of these plants by treatment with the homologous systemin. As in the tomato, in potato, black nightshade, and bell pepper plants, prosystemin homologs appear to function as precursors of systemic wound signals.

Amino Acid Sequence↗
PubMed1998

Intravenous administration of oral N-acetylcysteine.

OBJECTIVE: To report the indications and adverse events associated with administration of the oral N-acetylcysteine preparation by the intravenous route. DESIGN: Retrospective consecutive case series analysis of 226,720 Toxic Exposure Surveillance System data sheets from a certified regional poison center during the period January 1, 1992 through December 31, 1993. SETTING: A regional poison center certified by the American Association of Poison Control Centers. PATIENTS: Seventy-six patients treated with the oral N-acetylcysteine solution by the intravenous route. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We report the indications and adverse events associated with the intravenous administration of the oral N-acetylcysteine preparation. Four (4/76, 5.3%) patients developed adverse events attributable to N-acetylcysteine. None of these events involved hemodynamic, cardiovascular, or pulmonary effects. All reactions occurred during infusion of the initial N-acetylcysteine dose. There were three (3/76, 3.9%) deaths overall; however, they were not attributable to the intravenous administration of the oral N-acetylcysteine preparation. CONCLUSIONS: Intravenous administration of the oral N-acetylcysteine preparation appears to have limited adverse effects and offers another mechanism of delivery of the potentially lifesaving N-acetylcysteine when oral administration is not possible.

Acetaminophen↗
PubMed1998

Trabeculectomy survival with and without intra-operative 5-fluorouracil application in an Asian population.

PURPOSE: To define and compare the trabeculectomy survival with regard to intra-ocular pressure (IOP) control without further surgery or anti-glaucoma medication n an Asian population. METHODS: A retrospective review of two consecutive groups of patients who had trabeculectomy surgery in a university eye department setting. The first group of patients (group A) did not receive any adjunctive 5-fluorouracil (5-FU), while the second group (group B) had intra-operative sponge application of 5-FU. Only the first trabeculectomy of patients who had bilateral trabeculectomy and the first trabeculectomy performed in patients who had repeated surgery was analysed. Combined procedures were excluded. Survival analysis was performed using the Kaplan-Meier product limit method. RESULTS: Eighty-nine patients (51 in group A and 38 in group B) were studied, with a mean follow up of 37.5 and 27.0 months, respectively (P = 0.014). There were no statistical differences in age, gender, mean pretreatment IOP, pre-operative medication, proportion of patients with previous ocular surgery, or proportion of primary compared with secondary glaucoma between the two groups. The probability of trabeculectomy survival (IOP < 22 mmHg without additional medication/surgery) at 12 and 36 months was 54.3 and 36.4%, respectively, in group A and 75.8 and 65.8%, respectively, in group B. The differences in survival were significant (P = 0.006, log rank test). CONCLUSIONS: Our experience with trabeculectomy survival in the Asian population showed poorer success when compared with Caucasian populations reported by other investigators. The survival of trabeculectomy surgery was improved significantly with intra-operative 5-FU. There may be justification for advocating a more liberal use of intra-operative 5-FU in such a population.

Administration, Topical↗
PubMed1998

The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice.

In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.

Animals↗
PubMed1997

Distribution and substrate properties of agrin, a heparan sulfate proteoglycan of developing axonal pathways.

The distribution and substrate properties of agrin, an extracellular matrix heparan sulfate proteoglycan (HSPG), was investigated in the developing chick nervous system by immunocytochemistry, Western blotting, and in neurite outgrowth assays. By comparing the distribution of agrin with that of laminin-1, merosin (laminin-2), neurofilament, and neural cell adhesion molecule (NCAM), it was found that throughout development, agrin is a constituent of all basal laminae. From embryonic day (E) 4 onwards, agrin is also abundant in axonal pathways of the central nervous system, such as the optic nerve, the tectobulbar pathway, the white matter of the spinal cord, and the marginal and the molecular layers of the forebrain and the cerebellum. The abundance of agrin in brain decreases from E13 onwards. In the peripheral nervous system, agrin is present throughout development as a constituent of the Schwann cell basal laminae. Western blots confirmed the immunocytochemical data, showing maximum expression of agrin occurs during the early to medium stages of brain development. Western blots also showed that in mouse and human brain, agrin exists as an HSPG. Purified agrin did not support neurite outgrowth, rather it inhibited retinal neurite extension on mixed agrin/merosin substrates. Despite the fact that agrin, when used as a substrate inhibited neurite outgrowth, its temporal and spatial overlap with growing axons suggests that agrin has a supportive role in the development of axonal pathways, possibly as a binding component for growth factors and cell adhesion proteins.

Agrin↗
PubMed1995

Isolation of the anthropogenic compound fluoranthene in a screening of Chinese medicinal plants for antiviral compounds.

Thirty-one species of medicinal plants used in the treatment of diseases of viral origin in Yunnan Province of China were assayed for inhibition of Sindbis and murine cytomegalovirus in mammalian cell cultures. Sixteen species displayed antiviral activity. A compound, which exhibited long wavelength UV-mediated antiviral activity, was isolated from leaves and twigs of Elsholtzia ciliata (Lamiaceae) using bioassay-guided fractionation and identified as the polycyclic aromatic hydrocarbon, fluoranthene. The discovery of an anthropogenic photosensitizer with antiviral activity in a plant has implications in studies of plants as sources of bioactive constituents.

Antiviral Agents↗
PubMed1994

Hypocrellin, from Hypocrella bambuase, is phototoxic to human immunodeficiency virus.

Hypocrellin, a photodynamic perylene quinonoid isolated from the Chinese medicinal fungus Hypocrella bambuase, was evaluated for antiviral activity against the human immunodeficiency virus (HIV-1). Hypocrellin was phototoxic to HIV-1, almost as good as the structurally similar plant pigment hypericin, and like hypericin its activity required visible light. In contrast peroxyhypocrellin had little or no effect on the virus.

3T3 Cells↗