Pattern of Epstein-Barr virus association in childhood non-Hodgkin's lymphoma: experience of university of malaya medical center

The pattern of childhood non-Hodgkin's lymphoma (NHL) usually differs in adults. The most common subtypes are lymphoblastic, Burkitt's and anaplastic large cell lymphoma. Recent data indicate that a higher risk of developing lymphoma is associated in children of certain ethnic origins. The difference is probably related to the underlying etiological factors of these diseases, and Epstein-Barr virus (EBV) is a strong candidate. The present study aims to determine the disease pattern of childhood lymphomas in the University Hospital Kuala Lumpur, for a direct comparison to the reported data of adults from the same medical center. A total of 69 and 34 childhood NHL and Hodgkin's lymphomas, respectively, were retrieved. The most common subtypes were lymphoblastic (23 cases), Burkitt's (25 cases) and anaplastic large cell lymphomas (9 cases). Epstein-Barr virus association was more prevalent in B-cell (23%) than T-cell (12%) lymphomas. The most common EBV-associated tumor was Burkitt's lymphoma, and there was an increased risk of EBV association for Burkitt's lymphoma in Chinese patients. In conclusion, the pattern of childhood lymphoma in Malaysia is relatively similar to children elsewhere in the world. The EBV association of B- and T-NHL differs between children and adults from the same medical center because of differences in the subtype composition in these two age groups.     

Steroidogenic acute regulatory protein: its presence and function in brain neurosteroidogenesis

Neurosteroids are synthesized de novo and involved in a variety of physiological functions in the central and peripheral nervous systems. Although the steroidogenic acute regulatory protein (StAR) plays an essential role in the steroidogenesis of peripheral endocrine glands, its presence and role in the brain had been previously questioned because of difficulties in detecting it. However, a number of recent studies have confirmed the presence of StAR in rodent and human brains. Moreover, there is evidence suggesting that StAR plays a role in steroidogenesis in the brain, as it does in peripheral endocrine organs. The present review presents data regarding the presence and role of StAR in brain steroidogenesis, demonstrating the essential characteristics of the protein.     

Misoprostol in labour induction of term pregnancy: a meta-analysis

Objective To evaluate the efficacy and safety of misoprostol in term labour induction. Data sources Data from published English and Chinese literatures about misoprostol in term labour induction were identified from Medline and CBMdisk (using the search terms “misoprostol” and “labour induction”) before 2001; hand searches of reference lists of original studies and reviews (including meta-analyses) and contact with investigators in this field before 2001. Study selection Studies were included if they had data on misoprostol and labour induction. Altogether 623 articles were found and 124 were admitted, including 19 287 cases. Data extraction Data were collected on efficacy and incidence of side-effects of misoprostol and oxytocin. Data were checked for consistency within the published articles and converted into a standard format for incorporation into a central database. Data synthesis The average successful induction rate, rates of caesarean section; incidence of tachysystole, hypertonus of uterus and precipitous labour, and rates of meconium stained amniotic fluid between the misoprostol and oxytocin groups were significantly different (P<0.05). There were no significant differences between the two groups concerning the average interval from the administration of misoprostol and oxytocin to the onset of labour, duration of the total stage of labour, incidence rate of foetal distress, neonatal asphyxia (1-minute Apgar score≤7), postpartum haemorrhage or amount of blood loss in postpartum.Conclusions Misoprostol is a superior agent over oxytocin on the induction of term labour, but its application might increase the risk of precipitatous labour, abnormal uterine contractions or meconium stained amniotic fluid. Therefore, the doasges and regimens of the agent need further investigation.     

Hypertension: pathophysiology and treatment

Arterial hypertension is a major cause of morbidity and mortalitybecause of its association with coronary heart disease, cerebrovasculardisease and renal disease. The extent of target organ involvement(i.e. heart, brain and kidneys) determines outcome. North Americanstudies have shown that hypertension is a major contributorto 500 000 strokes (250 000 deaths) and 1 000 000 myocardialinfarctions (500 000 deaths) per annum.     

Quantitative assessment of the cell penetrating properties of RI-Tat-9: evidence for a cell type-specific barrier at the plasma membrane of epithelial cells

Penetration of epithelial cells represents the rate-determining step for the absorption of many drugs and pharmaceutical macromolecules such as proteins and nucleic acid therapeutics. While the potential of using cell-penetrating peptides (CPPs) to facilitate absorption has been increasingly recognized, the mechanism of cell penetration and the uptake into certain cells have recently been called into question due to methodological artifacts. Therefore, the objective of this study was to quantitatively assess the ability of RI-Tat-9, a proteolytically stable CPP, to penetrate epithelial cell monolayers. The permeability of RI-Tat-9 with two epithelial cell lines, Madin-Darby canine kidney (MDCK) and Caco-2 cells, was comparable to the leakiness of the respective intact monolayers. Microscopic imaging showed that fluorescence-tagged RI-Tat-9 did not enter these cells, further supporting a paracellular transport mechanism. Although insufficient data were generated in these studies to generalize the observed phenomenon, the entry of RI-Tat-9 into nonepithelial T lymphocytic MT2 cells, possibly by endocytosis, suggested that a cell type-specific barrier might exist that controlled uptake of RI-Tat-9 by cells. Compared to that in MT2 and HeLa cells, the active uptake of the peptide into MDCK monolayers was much slower and showed no dependence of cell energy. Furthermore, the equilibrium binding of RI-Tat-9 to MDCK cells at 0 degrees C was indicative of an interaction with a nonspecific receptor. A correlation between binding density and concentration difference across a leaky separation barrier suggested that repulsion of free peptide molecules by bound peptide molecules at the MDCK monolayer surface may be significant at micromolar concentrations. The results of this study quantitatively show that Tat CPP uptake into two commonly used epithelial cell types is minimal and possibly cell type-specific. Implications for Tat CPP-assisted drug delivery are discussed.     

Vaccination-induced autoimmune vitiligo is a consequence of secondary trauma to the skin

A major concern for cancer vaccines targeting self-tumor antigens is the risk of autoimmune sequelae. Although antitumor immunity correlates with autoimmune disease in some preclinical models, the mechanism(s) linking antitumor immunity and subsequent autoimmune pathology remain(s) to be determined. In the current study, we demonstrated that intradermal (i.d.) immunization with a recombinant adenovirus (Ad) expressing the murine melanoma antigen tyrosinase-related protein 2 (AdmTrp-2) results in a moderate level of tumor protection against the B16F10 murine melanoma without any vitiligo. Similar immunization with an Ad encoding human Trp-2 (AdhTrp-2) resulted in 50-fold greater protective immunity and produced vitiligo in all of the mice, suggesting that the development of autoimmunity may reflect the potency of the vaccine. Interestingly, delivery of AdhTrp-2 by i.m. injection generated protective immunity comparable with that seen in mice that received the vaccine by the i.d. route, but none of the recipients in the i.m. group developed vitiligo. The cellular and humoral responses in the i.m. immunized mice were greater than in the i.d. group; therefore, the lack of vitiligo was not caused by reduced efficacy of the vaccine. These results led us to hypothesize that vaccine-induced vitiligo was associated with local inflammatory responses. Mice immunized i.m. with AdhTrp-2 did develop vitiligo when they subsequently were injected i.d. with either a control Ad vector or complete Freund's adjuvant, suggesting that vitiligo is initiated by some form of trauma within the skin. Our data demonstrated that autoimmune pathology is not an unavoidable outcome of effective cancer vaccines directed against self-tumor antigens.     

A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet

The ketogenic diet (KD) is an effective therapy for medically intractable epilepsy, but its anticonvulsant mechanisms are unknown. Few studies to date have addressed the molecular changes following treatment with a KD. In the present study, we fed juvenile rats either a standard diet or a KD for 1 month, and then determined changes in hippocampal gene expression using cDNA microarray analysis (Clontech). To validate the microarray expression results, we also performed Northern blot and RT-PCR analysis on a small subset of affected genes. Among a total of 1176 cDNAs, 42 genes were strongly up- or down-regulated (>2-fold change over controls) by a KD. We found that the expression of mitochondrial ATP synthase beta subunit, mitochondrial ATP synthase D subunit (ATP5H) and mitochondrial ATP synthase beta subunit precursor (ATP5F) were especially increased in KD-treated group, whereas the KD down-regulated protein kinase C (PKC) beta and epsilon isoforms. Thus, the most prominent changes were seen in genes encoding proteins involved in mitochondrial metabolic and intracellular signal transduction pathways. Our data provide some insights into the complex cascade of cellular changes in the hippocampus induced by a KD, some of which may contribute to its anticonvulsant effects.     

The use of recombinant human epidermal growth factor (rhEGF) in a gentleman with drug-induced Steven Johnson syndrome

A case of drug-induced Steven Johnson syndrome in a gentleman is reported. Its course of treatment with rhEGF was compared to conventional treatment in historical control.