Biomedical subjects

A Wee

Publications and source records attributed to A Wee.

At least 37 records · Page 2Linked to original sources

PubMed1996

Animal tissue-polypyrrole hybrid biomaterials: shrinkage temperature evaluation.

The shrinkage temperature of animal tissue-polypyrrole hybrids have been evaluated. The results indicate that the tissue's shrinkage temperature behaviour is retained. The tissues do not appear to have been affected by surface layering with polypyrrole or poly(sodium 3-pyrrolyl-butanesulphonate) (PSPBS). The main influence on the shrinkage temperature appears to be the reaction conditions in producing the hybrids i.e. the solvent and the presence of FeCl3. Hybrids obtained from reactions where the solvent was acetic acid demonstrated irreversible denaturation giving a final lower shrinkage temperature than the original value. All tissues exposed to FeCl3 were found to have higher shrinkage temperatures. This has been attributed to transient coordination bonding between the metal ion and side groups on the amino acid. The single peak of PSPBS-tissue hybrids in acetic acid is probably associated with the effective penetration of the PSPBS into the tissue, permitting some interaction between the functionalities of the conducting polymer and collagen.

Alkanesulfonic Acids↗

PubMed1996

Hybrid biomaterials based on the interaction of polyurethane oligomers with porcine pericardium.

Hybrid biomaterials have been produced by the interaction of polyurethane oligomers with both fresh and glutaraldehyde-fixed porcine pericardium. The hybrid biomaterials so formed were translucent with occasional white streaks and/or spots, had increased stiffness (to touch) but remained pliable. No shrinkage temperature was detected for fresh porcine pericardium hybrid up to 100 degrees C compared to porcine pericardium (approximately 67 degrees C) and glutaraldehyde-fixed porcine pericardium (approximately 87 degrees C). Amino acid analysis of the fresh porcine pericardium hybrid showed a reduction in lysine content after active isocyanate-terminated polyurethane oligomers exposure, indicating cross-linking between the polymer and tissue. Histological examination of the hybrid material shows a thin grey coating on both surfaces of the tissue, implying at least surface cross-linking of the tissue with polyurethane. The results suggest that fresh porcine pericardium can be reacted with active isocyanate-terminated polyurethane oligomers to produce hybrid biomaterials with covalent bonding.

Animals↗

PubMed1996

Subcutaneously administered recombinant human beta-interferon in the treatment of chronic hepatitis B virus infection.

BACKGROUND: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. beta-Interferon treatment has been less well studied than alpha-interferon. METHODS: The efficacy and tolerability of a 6-month course of subcutaneously administered human recombinant beta-interferon (rINF-beta ser) was studied and the results of a low-dose regime compared with a high-dose regime. Twenty patients (17 men and three women), aged 24-54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen-positive with detectable HBV-DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low-dose group received 6 x 10(6) U/dose and the high-dose group received 30 x 10(6) U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months. RESULTS: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side-effects. HBV-DNA decreased in all patients during treatment, demonstrating the anti-viral efficacy of rINF-beta ser, and was undetectable in 20 and 40% of patients receiving low-dose and high-dose regimes, respectively, at the end of 6 months treatment (P = N.S.). One year after completion of treatment, HBV-DNA was undetectable in 50 and 30% of patients in the low-dose and high-dose groups, respectively (P = N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an antihepatitis B 'e' antigen at the end of 18 months. CONCLUSION: This study shows that subcutaneously administered rINF-beta ser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.

Adult↗

PubMed1996

An immunohistochemical study of p53 protein in cervical intraepithelial neoplasia and squamous cell carcinoma.

p53 mutations are known to occur frequently in human cancers where they are considered to be an important event in the stepwise progression towards malignant transformation. It is therefore interesting to compare p53 expression in the uterine cervix for non-neoplastic/metaplastic squamous epithelium, cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma. One hundred and nineteen biopsied and resected specimens of the uterine cervix were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Histologically these could be categorized into non-neoplastic/dysplastic conditions, including condyloma (34 cases), CIN 1-3 (66 cases) and invasive squamous cell carcinoma (19 cases). Fifty eight per cent (11/19) of the invasive squamous cell carcinomas and 11% (7/66) of the CIN stained positively for p53. Except for 3 cases of invasive squamous cell carcinoma, there was only sporadic intranuclear staining of less than 5% of the cells. No staining was observed in all non-neoplastic/metaplastic squamous epithelial cells. The pattern of p53 staining is significantly different for all 3 categories. However it is undetermined as to whether the positive immunoperoxidase staining is a direct consequence of p53 gene mutation or otherwise.

Antibodies, Monoclonal↗

PubMed1996

Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma.

Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG --> AGT (Arg --> Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT --> AAA (Asn --> Cys) transversion at codon 200 in TONG/HCC, an AAG --> GAG (Lys --> Glu) transition at codon 139 in HCC-T, a CAT --> CGT (His --> Arg) transition at codon 214 in SC4, and a CCC --> CTC (Pro --> Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.

Animals↗

PubMed1996

Primary biliary cirrhosis--an uncommon disease in Singapore.

Primary biliary cirrhosis (PBC) is uncommon in Singapore. Twelve consecutive patients with PBC were seen between 1987 and 1994 at the National University Hospital. Eleven were women and the mean age at presentation was 53 years. Three patients presented with pruritus and jaundice whilst three had decompensated cirrhosis. The remaining six patients had no symptoms attributed to their liver disease when first detected, three of them presented with associated conditions including sicca syndrome and interstitial lung fibrosis, lichen planus, and carcinoma of breast. All patients had elevated serum alkaline phosphatase and positive anti-mitochondrial antibodies. Liver histology (10/12) showed Stage II disease (2), Stage III (5) and Stage IV (3). Three patients also had co-existing gall bladder stones but their endoscopic retrograde cholangiograms were normal. The mean follow-up period was 32.6 months and four patients died during follow-up. The only male patient had liver transplantation, two patients had symptomatic treatment while the rest were treated with ursodeoxycholic acid. In conclusion, local patients tended to presented relatively early in the course of the disease with 50% being asymptomatic and in the precirrhotic Stages.

Adult↗

PubMed1995

Chili protects against aspirin-induced gastroduodenal mucosal injury in humans.

Capsaicin, the pungent ingredient of chili, has a gastroprotective effect against experimental gastric mucosal injury in animals. Such an effect has not, however, been documented in humans to date. Eighteen healthy volunteers with normal index endoscopies underwent two studies four weeks apart. Each subject took 20 g chili orally with 200 ml water in one study and 200 ml water in another study. In each case this was followed half an hour later by 600 mg aspirin BP with 200 ml water. Endoscopy was repeated 6 hr later. Gastroduodenal mucosal damage was assessed by a previously validated scoring system. The median gastric injury score after chili was 1.5 compared to 4 in the control group (P < 0.05), demonstrating a gastroprotective effect of chili in human subjects.

Adult↗

PubMed1995

In situ polymerization of pyrrole in animal tissue in the formation of hybrid biomaterials.

Porcine pericardium was impregnated with pyrrole or its derivative, sodium 4-(3-pyrrolyl)butanesulphonate (SPBS), by soaking the animal tissue in the monomer. Subsequent in situ chemical polymerization of the monomer-rich tissue using FeCl3 as initiator produced black polypyrrole-tissue hybrid biomaterials. The rate and extent of polymerization was found to be greater in 0.5 M acetic acid than in Hepes-buffered saline (HBS) and also greater for SPBS than for pyrrole. However, better tissue integrity was obtained for polymerization in HBS. Histological examination showed that the monomers do not permeate through the entire tissue, restricting polymerization to the surface layers of the tissue. The samples so formed do not exhibit detectable electrical conductivity.

Acetates↗

PubMed1995

Codon 249 mutation of the p53 gene is a rare event in hepatocellular carcinomas from ethnic Chinese in Singapore.

The present study characterised p53 mutations in 44 hepatocellular carcinomas (HCCs) from Chinese patients residing in a high-incidence area. Twelve point mutations (27%) were detected in tumour tissues using single-strand conformation polymorphism analysis followed by direct DNA sequencing. Remarkably, no mutations were observed at codon 249. This is in contrast to HCCs from other high HCC incidence areas with endemic aflatoxin exposures, in which codon 249 is a mutational hot spot. It is therefore suggested that risk factors other than dietary exposure to aflatoxin may contribute to the high HCC incidence in Singapore.

Adult↗

PubMed1995

Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha-interferon with steroid priming.

BACKGROUND: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pretreatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. METHODS: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. RESULTS: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. CONCLUSION: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.

Adult↗

PubMed1995

Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli.

Administration, Topical↗

PubMed1995

p53 expression in hepatocellular carcinoma in a population in Singapore with endemic hepatitis B virus infection.

AIMS: To study the expression and clinical significance (if any) of p53 protein in hepatocellular carcinomas (HCC) arising in a population with endemic hepatitis B virus (HBV) infection. METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin was embedded histological sections of 46 HCC cases using an antihuman p53 monoclonal antibody; serial sections were also stained for hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and alpha fetoprotein (AFP). Nuclear p53 staining was assessed according to intensity (absent, weak or strong) and extent (< 5%, 6-25%, 26-50%, and > 50%) of positive cells. Tissue HBsAg, HBcAg and AFP were recorded as absent or present. RESULTS: The p53 protein was expressed in 35% (16 of 46) of HCCs; the positive rate in grade III/IV tumours (13 of 31; 42%) was higher than in grade I/II tumours (three of 15; 20%) but this was not statistically significant. HBsAg positive tumours showed almost the same proportion of p53 staining (11 of 29; 38%) as HBsAg negative ones (five of 17; 29%). CONCLUSIONS: The p53 protein was expressed in 35% of HCC cases. There was no statistically significant correlation between HBV infection and p53 protein expression. Similarly, there was no definite correlation between p53 positivity and tumour size, histological grade or vascular invasion.

Adult↗

PubMed1995

Mutations of the tumour suppressor gene p53 in colorectal and hepatocellular carcinomas.

The present study describes mutations of the tumour suppressor gene p53 in a local collection of colorectal and hepatocellular carcinomas (HCCs). Tumour DNA was extracted from both fresh and paraffin-embedded tissues and exons 5-8 of the p53 gene were amplified by polymerase chain reaction (PCR). Mutations were detected by single-strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. Of the 38 colorectal carcinomas and 42 HCCs examined, 15 (39%) and 13 (31%), respectively, showed p53 mutations. Two-thirds (10/15) of the mutations in colorectal carcinomas were base transitions with a predominance at CpG dinucleotide sites--a pattern characteristic to an endogenous process in cancer development. Three mutational hotspots at codons 175, 248 and 282 were also identified. Mutations did not correlate with histological grade, Dukes stage, or metastasis. However, tumours at the distal site of the colorectum showed a higher proportion of mutations than the proximal site. In the case of HCCs, majority (9/13) of the mutations were base transitions and no mutations were observed at codon 249. This is in contrast to results from other high-incidence areas such as Africa and China, where aflatoxin is believed to be a major aetiologic factor for liver cancers. The results therefore suggest that other risk factors, rather than dietary exposure to aflatoxin, may contribute to the high HCC incidence in Singapore.

Adenocarcinoma↗

PubMed1994

An immunohistochemical study of p53 protein in gallbladder and extrahepatic bile duct/ampullary carcinomas.

BACKGROUND: p53 mutations are known to occur frequently in human cancers, including gallbladder carcinoma. However, there has been no study of p53 expression in extrahepatic bile duct/ampullary carcinoma. Furthermore, gallbladder carcinoma is associated with cholelithiasis, whereas no such association is known for extrahepatic bile duct carcinoma, suggesting that they could arise from different pathogenetic mechanisms. METHODS: Twenty-four gallbladder carcinomas and 35 extrahepatic bile duct/ampullary carcinomas were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Both the extent and intensity of p53 protein staining were noted. RESULTS: Ninety-two percent of the gallbladder carcinomas stained for p53 protein compared with only 66% of the extrahepatic bile duct/ampullary carcinomas. The statistical significance was maintained even when the comparison was restricted to strong p53 staining in moderately to poorly differentiated adenocarcinomas (P < 0.05). Of the gallbladder carcinomas, poorly differentiated adenocarcinomas stained more strongly than well to moderately differentiated adenocarcinomas; the converse was true for extrahepatic bile duct/ampullary adenocarcinomas. CONCLUSION: The majority of gallbladder and extrahepatic bile duct/ampullary carcinomas stain for p53 protein. The incidence and pattern of staining is different, however, and supports the contention that these could be different tumors with differing etiologies and pathogenetic mechanisms.

Adenocarcinoma↗

PubMed1994

HLA-DR antigen expression in colonic adenomas and adenocarcinomas.

Previous studies have shown that malignant transformation is sometimes associated with the aberrant expression of HLA class II antigens. The functional significance of such aberrant expression is not known. Since HLA-DR antigen is expressed in normal colonic mucosa, it would be interesting to see if malignant transformation could result in the aberrant suppression of this antigen. Sixteen colonic adenocarcinomas, 29 colonic adenomatous polyps and 23 samples of normal colonic mucosa, including 9 cases of colonic mucosa adjacent to carcinoma, were stained immunohistochemically for HLA-DR antigen. The intensity and distribution of the antigen staining in the cytoplasm and luminal surface of the epithelial elements were analysed semiquantitatively. The lymphoplasmacytic infiltrate in the lamina propria was also evaluated. Cytoplasmic HLA-DR antigen expression was found to be significantly diminished in moderately and poorly differentiated adenocarcinomas but not in adenomas or well-differentiated adenocarcinomas. This suggests that the change in HLA-DR expression is not intrinsic to the neoplastic process but may merely be due to the fact that malignant cells, as they become less differentiated, tend to show alterations in their antigenic phenotype.

Adenocarcinoma↗

PubMed1994

Helicobacter pylori infection in children with recurrent abdominal pain.

Forty-eight patients with recurrent abdominal pain were studied endoscopically for the presence of gastritis and Helicobacter pylori infection. Fifteen of these children had histological evidence of gastritis with eight of them having concomitant H. pylori infection. The majority of those with H. pylori infection had severe degrees of acute following chronic gastritis.

Abdominal Pain↗

PubMed1994

Clinical importance of p53 protein in gall bladder carcinoma and its precursor lesions.

AIMS: To study the expression and importance (if any) of p53 protein in gall bladder carcinoma and its precursor lesions. METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin wax embedded histological sections with an anti-human p53 monoclonal antibody (DO-7; Dako Corporation M7001) (24 carcinomas, one adenocarcinoma in situ, six dysplasias, three adenomas and four cases of chronic cholecystitis). Invasive, in situ, and dysplastic areas as well as normal-looking epithelium were sought. Nuclear staining was assessed according to intensity and extent of positive cells. Both variables were graded on a scale of 1-3 and aggregate p53 scores were obtained (range: 0, 2-6). Only p53 scores of > or = 3 were regarded as significant. RESULTS: Clinically important amounts of p53 were expressed in 92% of invasive carcinomas, 86% of carcinoma in situ, and 28% of dysplastic areas. None of the adenomas contained clinically important amounts of p53. Normal epithelium, present in all the cases, did not express p53 except in one case of moderately differentiated adenocarcinoma (p53 score 3). In general, there was no difference in the prevalence of p53 protein expression between dysplasias associated with, and those unassociated with invasive disease. There was a tendency for higher grade carcinomas to express more p53 protein. CONCLUSIONS: The distribution of p53 protein in invasive carcinomas and the adjacent dysplastic and preinvasive lesions suggests that it is more commonly expressed than previously thought. The fact that p53 protein is also expressed in cases of dysplasia and carcinoma in situ unassociated with invasive malignancy lends further support to the contention that p53 gene mutations may have a role in the pathogenesis of gall bladder cancer. Expression of p53 protein may possibly be an indication of likely disease progression from dysplasia, to carcinoma in situ, to invasive disease.

Adenocarcinoma↗

PubMed1994

The expression of HLA-DR antigen in cervical neoplasia.

The purpose of this study was to evaluate the relationship between cervical neoplasia and HLA-DR antigen (class II antigen) expression. Seventy-seven formaldehyde-fixed uterine specimens comprising morphologically normal cervix (12), chronic cervicitis (10), cervical intraepithelial neoplasia (CIN) of various grades (42), and invasive squamous cell carcinoma (13) were studied for the degree and type of inflammation, and immunohistochemically for the HLA-DR antigen expression in the epithelium. The nonneoplastic ectocervical squamous epithelium was consistently negative for HLA-DR antigen, even in sections showing significant lymphoplasmacytic infiltration. We found HLA-DR antigen positivity in endocervical glandular epithelium, immature metaplastic squamous epithelium, CIN, and invasive carcinoma. In cases of CIN, the aberrant expression of the antigen generally corresponded to the level of dysplasia. Specific cells exhibiting koilocytic change were negative. All the cases of squamous cell carcinoma expressed the antigen, albeit variable in intensity and distribution. These findings suggest that aberrant HLA-DR antigen expression in the uterine ectocervix may be a consequence of dysplastic changes of the squamous epithelium that is maintained even after malignant transformation. On the other hand, HLA-DR positivity in immature metaplastic epithelium is probably a mere reflection of the fact that normal endocervical glandular epithelium can express the antigen.

Carcinoma, Squamous Cell↗