Loss of heterozygosity analysis of mouse pulmonary adenomas induced by coal tar

Manufactured gas plant (MGP) residues, commonly known as coal tars, were generated several decades ago as a byproduct of residential and industrial gas production from the distillation of coal. Previous short-term exposure studies have shown MGP residues to be tumorigenic in mouse liver and lung. In order to gain further insight into carcinogenesis by complex mixtures of environmental chemicals containing known carcinogenic polycyclic aromatic hydrocarbons, we investigated mouse pulmonary tumors for loss of heterozygosity (LOH) as a result of multiple exposure to MGP residues. Twenty mouse lung adenomas produced in (C57BL/6 x C3H)F1 hybrid mice and manually microdissected were selected to examine genome-wide allelic losses at 58 microsatellite loci. Regions of chromosomes 1, 4, 5, 8, and 11 were affected in 30-40% of tumors. The elevated rates of allelic imbalance in these chromosomes may indicate the location of unknown tumor suppressor genes significant to neoplastic transformation in mouse lung tissues. Laser capture microdissection-based LOH analysis of pulmonary adenomas showed that contamination of nonneoplastic tissues was not masking the allelic losses in the manually microdissected tumor analysis. The low frequency of chromosome instability in these tumors, measured by means of inter-simple sequence repeat PCR, suggests the presence of discrete regions of LOH instead of extensive structural rearrangements.     

A new prognostic model for testicular germ cell tumours

In univariate analyses of patients with metastatic testicular germ cell tumours (TGCT), both the International Germ Cell Consensus Classification (IGCCC) and serum lactate dehydrogenase (S-LD) isoenzyme 1 catalytic concentration (S-LD-1) significantly predicted survival. In complementary analyses of 81 patients with metastatic TGCT, S-LD and S-LD-1 classified the prognosis differently for 23 patients. In multivariate Cox hazard analyses of risk factors, only IGCCC and S-LD-1 predicted the prognosis (p=0.036, and p=0.0007, respectively). A new prognostic model based on prognostic information from main histology, IGCCC, and S-LD-1 changed the prognostic prediction by IGCCC for 19 patients (24%). Judged by to the area under the curve for receiver operation characteristics curves, the new model predicted five-years survival for the patients better than IGCCC and a modified version of the third edition of the TNM classification (p=0.025, and p=0.01, respectively). However, new studies should validate the new model before it is recommended as a general classification system of patients with metastatic TGCT.     

Acute reversible placental dysfunction and abnormal fetal heart rate at delivery

Acute placental dysfunction induced by malaria is characterized by umbilical artery resistance increase and cerebral artery resistance decrease during the crisis. The objective was to evaluate the sensitivity and specificity of fetal Doppler indices and crisis duration for predicting abnormal fetal heart rate (aFHR) at delivery several weeks after the crisis. Method: Every day during the crisis, the umbilical and cerebral resistance indices were measured by Doppler. These indices allowed evaluation of the amplitude of the fetal flow redistribution (C/U = cerebral resistance/umbilical resistance ratio), the duration of the flow redistribution period (i.e. crisis duration) and the Hypoxic index (HI) (mean %C/U change × crisis duration). Results: Population: 46 pregnancies. Mean duration of the flow redistribution period 8±3.2 days, mean C/U change −9%±6; Hypoxic index −86±75; prematures 48%; aFHR 30%). Hypoxic index >150 predicted occurrence of aFHR with high sensitivity and specificity (83%/88%). The presence of abnormal flow distribution (C/U<1.1) and the duration of the period with flow disturbance (>8 days) predicted aFHR at delivery with a sensitivity of 45 and 48% and a specificity of 82 and 84%. Conclusion: The Hypoxic index was more predictive of aFHR at delivery than the amplitude or the duration of the fetal flow redistribution triggered by placental insufficiency.     

Adenocarcinoma of the endolymphatic sac in children. A case report

We report a case of an adenocarcinoma of the endolymphatic sac in a 13 years old child, which was fortuitously discovered at the time of radiological investigation of growth delay. Arising from the end of the endolymphatic sac, this rare tumour shares a similar clinic expression with other cerebellopontine angle pathologies. Radiological investigation reveals a moth eaten appearance to the posterior temporal bone and specific bony inclusions. With MRI there is an intense and/or intermediate signal on T1, a hyper signal on T2 and T1 enhancement with injection of gadolinium. Treatment is surgical and local recurrences are not uncommon. After histological confirmation, a search for Von Hippel-Lindau disease is mandatory because this tumour is not exceptional among this subset of patients. Diagnosis and therapeutic criteria will be highlighted by our case and a review of the literature.     

Clear and compelling evidence: the Polish tribunal on abortion rights

On 25 July 2001 the Polish Federation for Women and Family Planning organised a Tribunal on Abortion Rights in Warsaw, to publicize the negative consequences of the criminalization of abortion in Poland. A panel of Polish and foreign experts heard the testimonials of seven Polish women's experiences under the 1993 "Anti-Abortion Act". Only two of the seven women were able to tell their stories in person. One died in 2001, at the age of 21, of an unsafe abortion. One is legally blind after having carried her last pregnancy to term. One is in prison for infanticide, which in all likelihood was committed by her boyfriend. National and foreign journalists were in attendance, as well as observers from all walks of life--writers, students, mothers, activists, feminists, husbands. The evidence was clear and compelling. Restrictive abortion laws make abortion unsafe by pushing it underground, endanger women's health, create a climate where even those services that are allowed by law-become unavailable, and contravene standards set by international human rights law. The restrictive abortion law in Poland has not increased the number of births; it has only caused women and their families suffering. The Tribunal brought the issue of abortion into the media prior to an election campaign and galvanised Polish and other Eastern European women's groups to become more active in defence of abortion rights.     

Development of normal retinal organization depends on Sonic hedgehog signaling from ganglion cells

The adult retina is organized into three cellular layers--an outer photoreceptor, a middle interneuron and an inner retinal ganglion cell (RGC) layer. Although the retinal pigment epithelium (RPE) and Müller cells are important in the establishment and maintenance of this organization, the signals involved are unknown. Here we show that Sonic hedgehog signaling from RGCs is required for the normal laminar organization in the vertebrate retina.     

Virus-like particles: a new family of delivery systems

The development of antiviral vaccines has almost exclusively been based on live attenuated vaccines up until now. However, the efficacy of HBsAg particles as an antiHBV vaccine has clearly demonstrated that protective antiviral immunity can be achieved by other strategies. Virus-like particles formed by structural proteins were proven to be highly immunogenic and capable of inducing protective immunity against various viral infections in preclinical studies. Clinical trials using virus-like particles confirmed their safety and immunogenicity. Moreover, chimeric virus-like particles carrying foreign peptidic sequences were shown to elicit potent B- and T-cell responses. Virus-like particles formed by a fusion protein between the HBsAg and the circumsporozo?te surface protein are safe and immunogenic in volunteers and induce a partial protection against natural Plasmodium falciparum infection.     

Primary biliary cirrhosis accompanied by CREST syndrome

CREST syndrome, a relatively benign, slowly progressive variant of systemic scleroderma consists of calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Although the association of this syndrome with primary biliary cirrhosis (PBC) is recognized in women, it has never been described in a man. We report the rare case of a male patient with CREST syndrome accompanied by PBC, manifested by acute cholecystitis and mild jaundice. The association of the two conditions is clinically and etiologically important. Clinicians must be aware of this association, sincethe clinical features of CREST syndrome may be mild and may be thought to be complications of the underlying liver disease.     

Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*

Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki) relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively.