Telomerase reactivation is an early event in laryngeal carcinogenesis.

The exact role and timing of reactivation of telomerase, a key enzyme implicated in cellular immortalization and transformation in the multistep process of laryngeal carcinogenesis, is still unknown. We attempted to (1) determine that quantitative differences exist in the levels of telomerase catalytic subunit (hTERT) mRNA expression among different grades of laryngeal epithelial abnormalities classified according to the Ljubljana classification; (2) determine that telomerase reactivation is an important, most probably early event in laryngeal carcinogenesis; and (3) analyze whether the relative quantity of hTERT mRNA can be used as a molecular biomarker in the early detection of precancerous lesions. The relative quantity of hTERT mRNA, expressed as an hTERT index, was analyzed in 140 frozen laryngeal tissue specimens representing different morphological stages of laryngeal carcinogenesis by using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. The presence and relative quantity of hTERT mRNA in laryngeal epithelium increases progressively with the degree of epithelial abnormalities. hTERT mRNA was detectable in 1/15 normal laryngeal epithelia (7%, mean hTERT index 0.02), 3/15 simple hyperplasias (20%, mean hTERT index 0.09), 10/27 abnormal hyperplasias (37%, mean hTERT index 0.18), 9/12 atypical hyperplasias (75%, mean hTERT index 0.74), 8/9 intraepithelial carcinomas (89%, mean hTERT index 1.82), and 53/62 invasive laryngeal squamous cell carcinomas (85%, mean hTERT index 2.51). Statistical analysis revealed two groups of laryngeal epithelial changes with significant differences in the levels of hTERT mRNA expression (P <.0033): (1) normal and reactive hyperplastic laryngeal epithelium (simple and abnormal hyperplasia) and (2) atypical hyperplasia (precancerous lesion), intraepithelial and invasive laryngeal squamous cell carcinoma. The results of the present study suggest that telomerase reactivation is an early event in laryngeal carcinogenesis, detectable already at the stage of precancerous laryngeal epithelial changes. Nevertheless, other genetic abnormalities appear to be necessary for progression of these epithelial abnormalities toward invasive laryngeal squamous cell carcinoma.     

Abnormalities of cholesterol metabolism in autism spectrum disorders.

Although Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al., 2001; Am J Med Genet 98:191-200.], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated (1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and (2) the type and incidence of other sterol disorders in the same group. Using gas chromatography/mass spectrometry, cholesterol, and its precursor sterols were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dl, which is below the 5th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD.     

Polymerization of 3,3-bis (chloromethyl) oxetane catalyzed by i-Bu3Al in bulk. I. The conditions of high polymer formation

The high temperature (up to 220°C.) polymerization of 3,3-bis(chloromethyl)oxetane catalyzed by i-Bu₃Al was investigated. The conversion-time curves are of the autocatalytic type and the molecular weight increases lineary with conversion up to the point at which for lower temperatures, e.g. 60–80°C., the whole polymer becomes insoluble. An alternative explanation of this phenomenon is proposed; the formation of insoluble product is related to the entanglement of macromolecules of very high molecular weight and or macrocycle formation in the degradative chain transfer to polymer. The phenomenon of insoluble products formation was never observed at higher temperatures (> 150°C.). The dependence of molecular weight on catalyst and impurity concentrations as well as on the polymerization temperature was investigated. It was shown that the high molecular weight product (\documentclass{article}\pagestyle{empty}\begin{document}$\overline {DP}$\end{document} = 1000–1500) can be produced at 180–220°C. even at rather high impurity level.     

Chain transfer to ethers in the 3,3-bis(chloromethyl)oxetane polymerization catalyzed by Al(iso-C4H9)3

In the polymerization of 3,3-bis(chloromethyl)oxetane catalyzed by Aliso-C₄H₉/water catalyst, according to the previously reported data (FURUKAWA, SAEGUSA et al.) insoluble polymers are formed. Although neither the exact mechanism of oxetanes polymerization in the presence of AIR₃/H₂O catalysts nor the nature of the insoluble polymers are known it is possible to use chain transfer agents to obtain perfectly soluble polymers. The addition of low molecular weight ethers (C₂H₅)₂O, (n-C₄H₉)₂O, (Allyl)₂O, 1,4-dioxane, (β-ClC₂H₄)₂O, CH₃OPh, and (C₆H₅)₂O in low concentrations leads to the formation of soluble polymers with a very large range of mol. wts. (up to 10⁶). The chain transferabilities of ethers increase with their proton-attracting powers (basicity). In the presence of a chain transfer agent the kinetics of polymerization virtually changes. On the basis of the discussion of the general kinetic behaviors of the system and the dependence of D?P? on conversion it was deduced that in this type of polymerization long living species are formed.     

Tuberculosis of the tongue in a patient with disseminated pulmonary tuberculosis

A 51-year-old man, heavy cigarette smoker, a homeless alcoholic, with disseminated lesions in lungs and with ulceration and infiltration of the tongue is presented. Treatment with antibiotics was ineffective. He was admitted to the otolaryngological department because of suspicion of the tongue cancer. The histological examination of the tongue biopsy revealed tuberculous granuloma. In the pulmonological department, on admission the patient was cachectic, with massive oedema and ulceration of the tongue, and enlargement of the cervical lymph nodes. He was fed through the gastric tube. He had severe pain of the tongue demanding treatment with opiates analgesics. Chest x-ray revealed disseminated lesions in lungs. Antituberculous therapy was administered because of suspicion of tuberculosis of the tongue and lungs. During the treatment clinical improvement was observed. Tubercule bacilli were grown in the sputum culture after 6 weeks of observation. After 8 weeks of antituberculous therapy regression of lung lesions and healing of the tongue were observed. The patient continued treatment for 6 months in the Lung Disease Outpatient Clinic.     

How to perform high ultrasound examination of skin involvement among patients with systemic sclerosis – proposition of a unified protocol

IntroductionA fast and cheap method of skin assessment in systemic sclerosis (SSc) is an area of extensive research. Established in 1979, the Rodnan skin score is a palpation-based method used among clinicians. This method has some limitations, such as: examiner’s skills, subjective results, and no standardization. In the last few years researchers have been exploring ultrasound-based techniques as a possible tool for skin assessment among patients with SSc. The aim of the study is to develop a protocol of elastography-based skin imaging evaluation among patients with SSc.Material and methodsReview of the literature and own experience.ResultsProposition of elastography-based skin imaging protocol among patients with SSc.ConclusionsThe authors present a potential protocol of ultrasound-based examination of skin involvement among patients with SSc.     

Symptomatic hyponatraemia due to inappropriate antidiuretic hormone secretion following minor surgery

A rare case of the syndrome of inappropriate antidiuretic hormone secretion occurring after minor surgery is presented. A ten-year-old, previously healthy boy underwent general anaesthesia for detorsion and right orchiopexy. Throughout the operations, which lasted for one hour, he received 120 ml Ringer's lactate solution. The immediate postoperative period was uneventful. Twenty-two hours postoperatively he was found unconscious with generalized tonic-clonic seizures. Simultaneously obtained serum sodium concentration (121 mEq.L-1) serum osmolarity (265 mEq.L-1), urine sodium concentration (87 mEq.L-1) and urine osmolarity (525 mEq.L-1) suggested inappropriate antidiuretic hormone secretion which was confirmed by an elevated serum arginine-vasopressin (AVP) level of 14.5 pcg.ml-1 (normal 1-5 pcg.ml-1) measured by radioimmune assay. He was treated with a single iv dose of 30 mg furosemide and fluid restriction, which produced a gradual increase of his serum sodium concentration to normal within two days. He was well during the remainder of his hospitalization.     

Inhibition of cell cycle and induction of apoptosis by 2‐oxoheksyl isothiocyanate and alyssin in cell lines carrying various inherited BRCA1 mutations

An important aspect of the chemopreventive activity of isothiocyanates (ITC) is their ability to induce cell growth inhibition and apoptosis. In this study, the effect of two sulforaphane analogues, 2‐oxoheksyl isothiocyanate and alyssin, on lymphoblastoid cells, derived from people carrying four different germ‐line mutations in BRCA1 gene, was tested and compared to the effect on wild type cells. The mutations studied were: C61G; 3819del5; 4153delA, and 5382INSC. Changes in cell viability and density after 2‐oxoheksyl isothiocyanate and alyssin treatment were evaluated, as well as cell cycle progression, mitochondrial membrane potential changes, and phosphatidylserine externalization. Both isothiocyanates were shown to reduce cell viability and density in all cell lines tested, as well as the change in cell cycle phase's distribution. The response of cells to two ITC tested was various, as well as mutation type‐modulated. We found that change of cellular maintenance by chemopreventive agents can be modulated by single allele BRCA1 mutation. Drug Dev. Res. 65:84–92, 2005. © 2005 Wiley‐Liss, Inc.