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.     

High-power 1320-nm wafer-bonded VCSELs with tunnel junctions

A new long-wavelength vertical-cavity surface-emitting laser structure is described that utilizes AlGaAs-GaAs mirrors bonded to AlInGaAs-InP quantum wells with an intracavity buried tunnel junction. This structure offers complete wavelength flexibility in the 1250-1650 nm fiber communication bands and reduces the high free-carrier losses and bonded junction voltage drops in previous devices. The intracavity contacts electrically bypass the bonded junctions to reduce threshold voltage. N-type current spreading layers and undoped AlGaAs mirrors minimize optical losses. This has enabled 134/spl deg/C maximum continuous-wave lasing temperature, 2-mW room-temperature continuous-wave single-mode power, and 1-mW single-mode power at 80/spl deg/C, in various devices in the 1310-1340 nm wavelength range.     

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.     

FTIR characterization of heterocycles lumazine and violapterin in solution: effects of solvent on anionic forms

Fourier transform infrared (FTIR) spectra have been obtained from solution samples of the heterocycles uracil, lumazine, and violapterin and reveal interpretable carbonyl stretching frequencies. Spectra of conjugate bases of lumazine and violapterin demonstrate decreases in these carbonyl stretching frequencies upon ionization. Based on isotopic shifts from amide deuterated analogs, semiempirical QCFF/PI calculations were used to assign the vibrational frequencies in the region 1100-1800 cm-1 observed from samples in dimethylsulfoxide (DMSO) and aqueous solutions to specific normal modes. The observed deuterium shifts and the calculations suggest that, in some cases, N-H bending motions are coupled to the C=O stretching motions of the pyrimidine ring. These data suggest that for lumazine anions a change in solvent can significantly change the mixing of the N-H bending and C=O stretching vibrational motions. This implies that vibrational analysis for lumazine species in relatively noninteracting media like nonpolar solvents, mulls or pellets cannot necessarily be transferred to the system when it is dissolved in a polar, hydrogen-bonding solvent such as water. Although other explanations can be offered, our vibrational analysis suggests that the changes in normal mode composition of the predominantly C=O stretching vibrations of lumazine anion on going from dimethylsulfoxide to water solution are consistent with a change in the predominant tautomer of the heterocycle. This change appears to correspond to a shifting of the location of the remaining acidic proton to a different ring nitrogen atom. This interpretation is of interest in view of recent ab initio calculations which suggest that proton shifts may occur during the hydroxylation of lumazine as mediated by the enzyme xanthine oxidase.