Non-ionizing radiation exposure causing ill-health and alopecia areata.

Three cases of occupational exposure to radio-frequency and microwave radiation were seen at the out-patient clinic, Hospital Universiti Sains Malaysia. They presented with run-down symptoms of neck strain associated with throbbing headache, irritability, loss of appetite, fatigue, memory difficulties, and numbness of extremities. They also presented with alopecia areata which is felt to be causally linked to the radiation exposure.     

Histopathological analysis of hysterectomy specimens

The objective of this study was to explore the histopathological findings and the rate of removal of ovaries in hysterectomy specimens. This study took into account 328 hysterectomy specimens examined in the Department of Pathology, Mymensingh Medical College and in one private Pathology Laboratory in Mymensingh town from March to August, 2005. Formalin fixed paraffin embedded tissue sections stained with haematoxylin and eosin were examined under light microscope. Patients' age, parts of uterus examined and their histopathological findings were retrieved from laboratory records. The common histopathological findings were: chronic cervicitis (87.80%), leiomyoma (17.07%), uterine prolapse (16.72%), adenomyosis (3.96), non-specific endometritis (3.35%), squamous cell carcinoma of cervix (2.44%), endometrial polyp (2.44%), serous cystadenoma of ovary (2.44%) and endometrial hyperplasia (1.83%). Some of the specimens show more than one lesions in the body of uterus, of which coexistence of adenomyosis and leiomyoma was the most common. Neoplastic lesions in cervix were 4.27%, in body 16.92% and in ovaries 5.06%. Malignant neoplasms were found in cervix 71.43%, in uterine corpus 3.03% and in ovaries 25%. Ovaries of both sides were removed in 48.17% of total cases. Their median age was 45 years, lowest age 23 years and maximum age was 82. The rate of removal of both ovaries was found to be increasing with the increase of age. Only one case was found to be subtotal hysterectomy and others were total hysterectomy. The present study revealed that the most common histopathological cause of hysterectomy is chronic cervicitis. Most common neoplastic cause of hysterectomy is leiomyoma. The rationalities and the possible after effect of hysterectomy in sexual functions and other physiological impairment should be followed up.     

VNTR markers for qualitative evaluation of engraftment in unrelated cord blood transplantations

Allogeneic stem cell transplantation is a treatment option for malignant and non-malignant disorders in children. For children with no HLA-matched sibling or related stem cell donors, there is the option of unrelated cord blood donors. At the University of Malaya Medical Centre (UMMC) in Kuala Lumpur, the first unrelated cord blood transplantation (CBT) was performed in October 1997. All unrelated CBT performed in UMMC relied on cord blood units imported from overseas. DNA typing with variable number of tandem repeat (VNTR) loci was done to qualitatively evaluate engraftment in 15 unrelated CBT. In all the fifteen cases that were evaluated, molecular evidence of engraftment or non-engraftment correlated with the clinical findings.     

Establishment and characterization of Asian oral cancer cell lines as in vitro models to study a disease prevalent in Asia

We have established 3 cell lines ORL-48, -115 and -136 from surgically resected specimens obtained from untreated primary human oral squamous cell carcinomas of the oral cavity. The in vitro growth characteristics, epithelial origin, in vitro anchorage independency, human papilloma-virus (HPV) infection, microsatellite instability status, karyotype and the status of various cell cycle regulators and gatekeepers of these cell lines were investigated. All 3 cell lines grew as monolayers with doubling times ranging between 26.4 and 40.8 h and were immortal. Karyotyping confirmed that these cell lines were of human origin with multiple random losses and gains of entire chromosomes and regions of chromosomes. Immunohistochemistry staining of cytokeratins confirmed the epithelial origin of these cell lines, and the low degree of anchorage independency expressed by these cell lines suggests non-transformed phenotypes. Genetic analysis identified mutations in the p53 gene in all cell lines and hypermethylation of p16INK4a in ORL-48 and -136. Analysis of MDM2 and EGFR expression indicated MDM2 overexpression in ORL-48 and EGFR overexpression in ORL-136 in comparison to the protein levels in normal oral keratinocytes. Analysis of the BAT-26 polyadenine repeat sequence and MLH-1 and MSH-2 repair enzymes demonstrated that all 3 cell lines were microsatellite stable. The role of HPV in driving carcinogenesis in these tumours was negated by the absence of HPV. Finally, analysis of the tissues from which these cell lines were derived indicated that the cell lines were genetically representative of the tumours, and, therefore, are useful tools in the understanding of the molecular changes associated with oral cancers.     

Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene and the rate of cognitive decline in Alzheimer's disease

The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the regulatory regions of the apolipoprotein E (APOE) gene modify the well-established epsilon4-associated risk for Alzheimer's disease (AD). Sequencing of the APOE gene regulatory regions revealed four previously reported promoter SNPs and one novel SNP in the previously described macrophage enhancer (ME.1). In addition, we also studied the two classic allelic missense SNPs that define epsilon2/epsilon3/epsilon4 status in a case-control association study. Analysis of pair-wise linkage disequilibrium (LD) of the five regulatory region SNPs with classic APOE SNPs revealed a previously unreported 7 kb LD block covering the entire APOE gene, part of the promoter and 3' enhancer region. We report here that in a case-control association study (N=719) of the seven SNPs, the genotype at codon 112 captures all the information required to assess disease risk. To explore correlations with quantitative traits, 169 patients were studied in whom rates of cognitive decline were available. In addition to the epsilon4 allele, two regulatory region SNPs were associated with the rate of cognitive decline in AD patients. This study highlights the effect of APOE gene variation on risk of AD and rate of cognitive decline and demonstrates that a single SNP, which confers epsilon4 status, captures all of the risk of developing AD but two SNPs in the regulatory region may affect the rate of cognitive decline in AD patients.     

Influence of green tea on enzymes of carbohydrate metabolism, antioxidant defense, and plasma membrane in rat tissues

OBJECTIVE: Green tea, consumed worldwide since ancient times, is considered beneficial to human health. We hypothesized that green tea would enhance antioxidant defenses and specific metabolic activities of rat intestine, liver, and kidney to improve their functions. METHODS: The effect of green tea given to rats in the diet or drinking water for 25 d was determined on blood chemistry and on activities of enzymes of carbohydrate metabolism, brush border membrane, and antioxidant defense. RESULTS: Serum glucose, cholesterol, phosphate, and body weight decreased, whereas the activities of lactate and malate dehydrogenases and glucose-6- and fructose 1,6-bis-phosphatases increased in the intestine and kidney but slightly changed in the liver. Activity of glucose-6-phosphate dehydrogenase profoundly increased in the renal cortex but decreased in other tissues. Lipid peroxidation increased in the intestine and renal medulla and decreased in the renal cortex and liver; catalase increased in all tissues but the medulla. Superoxide dismutase activity decreased in the intestine but increased in renal tissues. Activities of brush border membrane enzymes in general increased in the intestine and kidney. CONCLUSION: Green tea consumption resulted in enhanced enzyme activities of carbohydrate metabolism and antioxidant defenses, which may lead to improved health.     

Serum selenium level and other risk factors for breast cancer among patients in a Malaysian hospital

Objective The aim of this study is to investigate the association between breast cancer and serum selenium level as well as other risk factors for breast cancer. Methods A matched case-control study was conducted in a hospital in Malaysia from July 2000 to January 2001 and from May 2001 to June 2001. Sixty-two newly diagnosed breast cancer patients were selected as the cases. Each control, selected from the same hospital population was matched to each case according to age, ethnic group, and menopausal status. Results The mean selenium concentration among the cases was significantly lower than that among the control. There was a significant association (p<0.05) between breast cancer and low selenium serum level, nulliparity (OR=5.5,95% CI=1.22 to 24.81), exposure to cigarette smoke (OR=2.2, 95% CI=1.04 to 4.65) and use of oral contraceptives (OR=3.0, 95% CI=1.09 to 8.25) as determined by the McNemar test. Multivariate analysis showed that nulliparity (OR=10.08, 95% CI=1.48 to 68.52) and use of oral contraceptives (OR=3.66, 95% CI=1.36 to 9.87) were associated with increased breast cancer risk. An increased selenium concentration contributes to a reduced risk of breast cancer (OR=0.89, 95% CI=0.84 to 0.94). Conclusion The results suggest that use of oral contraceptive pills, being nulliparous, and a low serum selenium level are associated with breast cancer.     

Evaluation of TSPO PET Ligands [<Superscript>18</Superscript>F]VUIIS1009A and [<Superscript>18</Superscript>F]VUIIS1009B: Tracers for Cancer Imaging

Purpose

Positron emission tomography (PET) ligands targeting translocator protein (TSPO) are potential imaging diagnostics of cancer. In this study, we report two novel, high-affinity TSPO PET ligands that are 5,7 regioisomers, [¹⁸F]VUIIS1009A ([¹⁸F]3A) and [¹⁸F]VUIIS1009B ([¹⁸F]3B), and their initial in vitro and in vivo evaluation in healthy mice and glioma-bearing rats.

Procedures

VUIIS1009A/B was synthesized and confirmed by X-ray crystallography. Interactions between TSPO binding pocket and novel ligands were evaluated and compared with contemporary TSPO ligands using 2D ¹H-¹⁵N heteronuclear single quantum coherence (HSQC) spectroscopy. In vivo biodistribution of [¹⁸F]VUIIS1009A and [¹⁸F]VUIIS1009B was carried out in healthy mice with and without radioligand displacement. Dynamic PET imaging data were acquired simultaneously with [¹⁸F]VUIIS1009A/B injections in glioma-bearing rats, with binding reversibility and specificity evaluated by radioligand displacement. In vivo radiometabolite analysis was performed using radio-TLC, and quantitative analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry.

Results

Both VUIIS1009A (3A) and VUIIS1009B (3B) were found to exhibit exceptional binding affinity to TSPO, with observed IC₅₀ values against PK11195 approximately 500-fold lower than DPA-714. However, HSQC NMR suggested that VUIIS1009A and VUIIS1009B share a common binding pocket within mammalian TSPO (mTSPO) as DPA-714 and to a lesser extent, PK11195. [¹⁸F]VUIIS1009A ([¹⁸F]3A) and [¹⁸F]VUIIS1009B ([¹⁸F]3B) exhibited similar biodistribution in healthy mice. In rats bearing C6 gliomas, both [¹⁸F]VUIIS1009A and [¹⁸F]VUIIS1009B exhibited greater binding potential (k ₃/k ₄)in tumor tissue compared to [¹⁸F]DPA-714. Interestingly, [¹⁸F]VUIIS1009B exhibited significantly greater tumor uptake (V _T) than [¹⁸F]VUIIS1009A, which was attributed primarily to greater plasma-to-tumor extraction efficiency.

Conclusions

The novel PET ligand [¹⁸F]VUIIS1009B exhibits promising characteristics for imaging glioma; its superiority over [¹⁸F]VUIIS1009A, a regioisomer, appears to be primarily due to improved plasma extraction efficiency. Continued evaluation of [¹⁸F]VUIIS1009B as a high-affinity TSPO PET ligand for precision medicine appears warranted.