Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

Background  

Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC.     

Tuberculous otitis media presenting as complications: report of 18 cases.

Tuberculous otitis media is a rare but treatable disease; delay in its diagnosis usually leads to complications. In the last 15 years we have come across 18 cases of tuberculous otitis media, which presented various intra- and extracranial complications. In the past, tuberculous otitis media had always been considered a discrete disease, but it is possible that tuberculosis may coexist or secondarily affect an already discharging ear. The following discussion illustrates the complications and clinical problems encountered in tuberculous otitis media.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.     

Growth, puberty and obesity after treatment for leukaemia

Final height, body proportions, pubertal growth and body mass index were studied retrospectively in 142 survivors of acute lymphoblastic leukaemia (ALL). Treatment consisted of combination chemotherapy and cranial irradiation (18 or 24 Gy). Significant standing height loss and disproportion, with a relatively short back, was seen in both radiation dose groups. Girls were more severely affected than boys. Pubertal growth was adversely affected, with a reduction in peak height velocity in both sexes. Puberty occurred early in girls but at the normal time in boys. Nearly half the group were obese at final height, with no significant difference in incidence between the sexes. The relative roles of cranial irradiation and chemotherapy in the disturbance of growth, puberty and body composition observed in survivors of childhood ALL remain unclear. The aetiology is almost certainly multifactorial, with radiation-induced growth hormone insufficiency, early puberty, steroids and chemotherapy all having a role.     

Renal transplantation and osteoporosis

A cross sectional study assessed the bone mineral density (BMD) of 20 young adult patients who received a renal transplantation in childhood. The BMD of the lumbar spine, mainly trabecular bone, and of the total body, mainly cortical bone, were measured and expressed as an SD score. Fourteen patients (70%) had a BMD SD score of the lumbar spine below -1, of whom six patients were below -2. Fifteen patients (75%) had a BMD SD score of the total body below -1, of whom seven patients were below -2, Both trabecular and cortical bone appeared to be involved in the osteopenic process. The cumulative dose of prednisone was inversely correlated to both lumbar spine and total body BMD SD score. In a multiple regression analysis the cumulative dose of prednisone appeared to be the only factor with a significant effect on BMD SD score. Most young adult patients who had received a renal transplantation in childhood had moderate to severe osteopenia. Corticosteroid treatment played a major part in the development of osteopenia in these patients.     

Interindividual differences in the concentration of 1-hydroxypyrene-glucuronide in urine and polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells after charbroiled beef consumption

Biological markers of internal dose and macromolecular dosefrom PAHs provide a potential means of assessing environmentalexposure to PAHs through inhalation, ingestion and percutaneousabsorption. In this study we examined the time course and interindividualvariation of 1-hydroxypyrene-glucuronide (1-OHP-gluc) excretionin urine and PAH—DNA adduct formation in peripheral whiteblood cells (WBCs) after charbroiled (CB) beef consumption.As a marker of internal dose, 1-OHP-gluc was measured in humanurine using immunoaffinity chromatography and synchronous fluorescencespectroscopy. PAH—DNA adducts were measured in WBCs byenzyme-linked immunosorbent assay (ELISA) in order to assessmacromolecular dose. Ten healthy non smoking males consumedidentical amounts of CB beef on five consecutive days. Multipleblood and urine samples were collected before, during, and afterthe feeding period. The morning after the first day of CB beefconsumption, individual urinary concentrations of 1-OHP-glucincreased 10- to 80-fold (range:2.0–16.6 pmol/ml urine)aboveprefeed baseline concentreations (0.23±0.11pmol/ml) inthe 10 subjects. 1-OHP-gluc concentration decreased to nearbaseline levels by 24–72 h after CB beef consumption ended.In contrast, PAH—DNA adducts in WBCs increased markedlyin only four of 10 subjects during or after CB beef consumption.Significant interindividual variation was observed for bothurinary 1-OHP-gluc concentration (P < 0.001 by Kruskal—Wallis)and PAH—DNA adduct levels (P < 0.005) during the feedingperiod. The mean urinary 1-OHP-gluc concentration for each subjectduring and immediately after (days 2–8) the feeding periodwas significantly correlated with their mean PAH—DNA adductlevel in WBCs during the same time period (Spearman r = 0.79,P<0.01). Evidence of segregation of the subjects into separateresponse groups based on level of urinary 1-OHP-gluc was observed,suggesting that discrete determaints may regulate the absorption,metabolism and/or excretion of ingested pyrene.