Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.     

Robustness issues in optimal control of unstable plants

This paper presents a robustness analysis of the optimal solution of the step tracking problem in a one-degree of freedom control architecture, for the discrete-time multivariable (MIMO) case. It is shown that the resulting closed loop becomes arbitrarily fragile, i.e. the sensitivity peak becomes arbitrarily large, for certain reference directions. The cause of this problem is that the optimal controller depends on the reference direction. The paper shows that this dependence can be eliminated with an alternative formulation of the optimal problem where the cost is averaged over all reference directions.     

XPS studies of directly fluorinated HDPE: problems and solutions

X-ray photoelectron spectroscopy (XPS) applied to the study of fluorinated polymer surfaces presents several problems related both to peak assignment and to degradation. In this work, we analyse extensively the question of XPS peak assignments in this kind of surfaces. We conclude that in this kind of surfaces using binding energy differences between fluorine and carbon is better than using absolute binding energies. Also a useful relation between fluorine photoelectron energy vs. polymer composition expressed through the atomic ratio fluorine/carbon (F/C) was found. A protocol for data treatment is proposed and applied to a XPS study of the degradation induced by X-ray on high-density polyethylene surfaces modified by direct fluorination. Results obtained for the degradation, namely the atomic ratio F/C obtained by two different methods, combined with angle resolved X-ray photoelectron spectroscopy (ARXPS) were used to study the fluorine concentration profile in depth, producing self-consistent results.     

Pentylenetetrazol causes polysynaptic responses to appear in the dentate gyrus

In a particular brain region specific changes in inhibition or excitation may be the basis of seizure initiation. Alternatively, changes in the balance of excitation and inhibition in the circuit, which may be detectable as polysynaptic responses may be more important indicators of epileptogenesis. That the appearance of polysynaptic responses precedes the initiation and, therefore, may be necessary for the onset of epileptiform activity in the hippocampal-parahippocampal circuit was tested using the chemical convulsant pentylenetetrazol. Excitation and paired-pulse inhibition were measured in CA1 and the dentate gyrus of the urethane-anaesthetized rat before and after administration of pentylenetetrazol. In addition, three polysynaptic responses were monitored. In both CA1 and the dentate gyrus, pentylenetetrazol, 100 mg/kg, caused a trend towards increased excitability and caused a relatively mild loss of inhibition. Two polysynaptic responses appeared in the dentate gyrus after the administration of pentylenetratrazol, both apparently mediated through the entorhinal cortex. A polysynaptic response of the CA1 pyramidal neurons to contralateral angular bundle stimulation was not observed. These experiments demonstrate that pentylenetetrazol will facilitate only the appearance of polysynaptic responses mediated through the entorhinal cortex. These results support the hypothesis that pentylenetetrazol has a specific action within the entorhinal cortex that may facilitate the synchronization and spread of epileptiform activity. These results are also consistent with the hypothesis that the appearance of polysynaptic responses may be necessary for the onset of epileptogenesis in the hippocampal-parahippocampal circuit.     

Peptide amidating activity in human bronchoalveolar lavage fluid

Monitoring respiratory epithelial biology may reveal individuals with incipient lung cancer. The expression of neuroendocrine (NE) markers in pulmonary epithelium is thought to be central to lung development, repair of injury and may contribute to carcinogenesis. In this study, we evaluate several candidate NE markers to determine the feasibility of prospective analysis of clinical specimens. The potential NE markers include the enzyme L-DOPA decarboxylase (DDC), the neuropeptide gastrin releasing peptide (GRP), and peptidyl-glycine alpha-amidating monooxygenase (PAM), the bifunctional enzyme responsible for the final bioactivation step of many neuropeptides. A comparison of PAM activity and DDC levels in 30 lung cancer cell lines indicated that peptide amidating activity may be an indicator of NE status. Bronchoalveolar lavage (BAL) fluid from subjects at risk of developing second primary lung cancer and from volunteers was obtained. The activity of the first PAM enzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), ranged from not detectable to 507 pmol/h/mg protein in 57 specimens. The second PAM enzyme, peptidylamidoglycolate lyase (PAL), ranged from not detectable to 414 pmol/h/mg protein in 56 specimens. Using cluster analysis by the average linkage method, a group of enzyme values with PHM greater than 230 pmol/h/mg protein was determined. Long-term follow-up of these patients for new second primary lung cancers may help to determine the potential predictive value of PAM detected in the BAL fluid.     

Laparoscopy-assisted and -prepared hysterectomy. A series of 80 cases

OBJECTIVE: Our objective was to determine the interest of laparoscopic assisted vaginal hysterectomy. STUDY DESIGN: Between January 1991 to december 1994, 80 patients had laparoscopically assisted vaginal hysterectomy. We reviewed with particular emphasis characteristic indications, complications. RESULTS: Eighty were performed as laparoscopically assisted vaginal hysterectomy. 14 patients (17.5%) had laparotomy conversion; because of size of uterus in 3 cases, suspected ovarian tumor in 3 cases. Pelvic adherences in 4 cases, urinary tract injuries in 1 case, hypercapnia in 1 case, hemorrhage in 2 cases. 9 patients experienced febrile morbidity and 1 urinary infection. 1 patient received 2 units of packed red blood cells. The hospital stay was 5 days for laparoscopically assisted vaginal hysterectomy versus 5.9 for laparotomic hysterectomy. CONCLUSION: Laparoscopically assisted vaginal hysterectomy offers a technique to convert certain abdominal hysterectomies into vaginal hysterectomies with a 17.5% laparoconversion rate.     

Compulsory notification of cysticercosis in Ribeir?o Preto-SP, Brazil

Cysticercosis is a severe public health problem in several regions of Asia, Africa and Latin America. Epidemiologic studies based on the frequency of cases observed in specialized neurology, neurosurgery and computed tomography services, at autopsy and in seroepidemiologic studies do not permit the determination of the true prevalence of the disease in the population. The objective of the present study was to investigate the prevalence of cysticercosis by compulsory notification. The coefficient of prevalence was 54 cases/100,000 inhabitants in the municipality of Ribeir?o Preto. The results also indicated that cysticercosis is not under control in our region since 21% of cases presented the active form of the disease. Compulsory notification proved to be a valuable resource for the epidemiologic study of cysticercosis, also permitting the mapping of more affected areas for a better direction of prevention strategies.