Mapping of a breast cancer tumor suppressor gene locus to a 4-cM interval on chromosome 18q21

DPC4 and DCC, putative tumor suppressor genes implicated in the genesis of several types of human cancer, lie on the long arm of human chromosome 18. We examined 200 primary breast cancers for allelic losses on chromosome 18, using 15 microsatellite markers distributed along the long arm. Allelic loss was detected most frequently (29-30%) at loci mapped to 18q21. Deletion mapping of the 34 tumors showing partial or interstitial deletions identified a commonly deleted region within the 4-cM interval flanked by D18S474 and D18S487 at 18q21.1-q21.3. Although this interval included the DPC4 and DCC genes, we excluded DPC4 from candidacy when polymerase chain reaction-single-strand conformation polymorphism analysis of each exon failed to detect abnormalities in any of the 54 breast cancers that exhibited loss of heterozygosity involving 18q. Allelic loss on 18q was found more frequently in tumors of the solid tubular histological type (24 of 55, 44%) than in other types (24 of 113, 21%) (P = 0.0049). The results suggest that a tumor suppressor gene located within the 4-cM region at 18q21, either DCC or another gene not yet identified, may play a role in the development of some sporadic breast cancers, particularly those of the solid tubular type.     

Infantile myofibromatosis located in the temporal bone

Infantile myofibromatosis (IM) is a proliferative disorder of infancy and early childhood characterized by the nodular or diffuse growth of lesions that are comprised of a mixture of mesenchymal elements. Intracranial involvement is reportedly rare, only eight such patients having been reported to our knowledge. We report on a 4-year-old boy with intracranial IM with a mass in his left temporal bone. A previous report on intracranial IM proposed that the underlying dura mater should be resected because of the possibility of early recurrence. At surgery in this case, the tumor was noted to be located in the bone itself and did not arise from the underlying dura. Therefore, the underlying dura mater and venous sinus were preserved. The follow-up MRI showed no sign of recurrences. It may not to be necessary to resect the dura mater in patients with intracranial IM.     

Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis

Continuous awareness of systemic mycosis in immunocompromised patients is important. Early diagnosis is based on (direct) histologal examination and CT scan. Since treatment should start as early as possible, there is usually no time to await results of tissue cultures. Systemic treatment with amphotericin B and aggressive surgical débridement should be performed as soon as possible, while the place of hyperbaric oxygen and G-CSF remains to be established. In addition to routine preventive measures, prophylactic intranasal application of amphotericin B seems to be of value.     

Atomic-layer-deposited silicon-nitride/SiO2 stack––a highly potential gate dielectrics for advanced CMOS technology

An extremely thin (2 monolayers) silicon nitride layer has been deposited on thermally grown SiO₂ by an atomic-layer-deposition (ALD) technique and used as gate dielectrics in metal–oxide–semiconductor (MOS) devices. The stack dielectrics having equivalent oxide thickness (T_eq=2.2 nm) efficiently reduce the boron diffusion from p⁺ poly-Si gate without the pile up of nitrogen atoms at the SiO₂/Si interface. The ALD silicon nitride is thermally stable and has very flat surface on SiO₂ especially in the thin (<0.5 nm) thickness region.An improvement has been obtained in the reliability of the ALD silicon-nitride/SiO₂ stack gate dielectrics compared with those of conventional SiO₂ dielectrics of identical thickness. An interesting feature of soft breakdown free phenomena has been observed only in the proposed stack gate dielectrics. Possible breakdown mechanisms are discussed and a model has been proposed based on the concept of localized physical damages which induce the formation of conductive filaments near both the poly-Si/SiO₂ and SiO₂/Si-substrate interfaces for the SiO₂ gate dielectrics and only near the SiO₂/Si-substrate interface for the stack gate dielectrics.Employing annealing in NH₃ at a moderate temperature of 550 °C after the ALD of silicon nitride on SiO₂, further reliability improvement has been achieved, which exhibits low bulk trap density and low trap generation rate in comparison with the stack dielectrics without NH₃ annealing.Because of the excellent thickness controllability and good electronic properties, the ALD silicon nitride on a thin gate oxide will fulfill the severe requirements for the ultrathin stack gate dielectrics for sub-0.1 μm complementary MOS (CMOS) transistors.     

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.     

Urinary bladder carcinoma was induced in a patient treated with cyclophosphamide for malignant lymphoma

A major responsibility of any Quality Assurance Unit (QUA) is to ensure data integrity. Errors made during data entry can lead to many problems in the study review process and decrease the quality, accuracy, and overall efficiency of data management. One technique that can reduce the number of data entry errors in computer data sets is the use of a dual entry data system. Currently available software allows creation of customized data entry screens that either closely resemble or duplicate the data collection forms used during studies. Two data entry operators enter data into two independent data sets. The use of an on-screen display that resembles the data collection form reduces the potential for keypunch errors. The two data sets can then be electronically compared. The comparison reports differences between the two data sets. When differences exist, the correct values can be determined by reference to the original data sheets and the two data files can then be corrected. Theoretically, the only key punch errors that will exist after making these corrections are when the two independent entry operators make the same exact data entry error. Typically, the time required for two people to enter data is minimal compared to the time required to manually identify and correct data entry discrepancies. With error-free data entry, we have found that electronic data quality, accuracy, and audit efficiency are improved at every subsequent step of data management, analysis, quality assurance auditing, and report generation.     

Effects of adrenomedullin and calcitonin gene-related peptide on contractions of the rat aorta and porcine coronary artery

1. Effects of adrenomedullin and alpha-calcitonin gene-related peptide (CGRP) on the contractions and cytosolic Ca2+ concentrations ([Ca2+]i) of the rat aorta and porcine coronary artery were investigated. Characteristics of the receptors mediating the effects of adrenomedullin and alpha-CGRP were also investigated. 2. Adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation in the rat aorta contracted with noradrenaline. The IC50 values for adrenomedullin and alpha-CGRP were 2.4 nM and 4.0 nM, respectively. The relaxant effects of these peptides were abolished by removal of the endothelium and significantly attenuated by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMMA, 100 microM), but not by a cyclo-oxygenase inhibitor, indomethacin (10 microM). 3. Adrenomedullin and alpha-CGRP increased the endothelial [Ca2+]i in the rat aorta with endothelium, whereas they did not change [Ca2+]i in the smooth muscle. 4. An antagonist of the CGRP1 receptor, CGRP (8-37), antagonized the relaxant effects of alpha-CGRP and the beta-isoform of CGRP (beta-CGRP) but not those of adrenomedullin in the rat aorta. 5. In the porcine coronary artery contracted with U46619, adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation with an IC50 of 27.6 and 4.1 nM, respectively. Removal of the endothelium altered neither the IC50 values nor the maximal relaxations induced by adrenomedullin or alpha-CGRP. When the artery was contracted with high K+ solution (72.7 mM), these peptides caused a small relaxation. 6. Adrenomedullin and alpha-CGRP increased cyclic AMP content and decreased the smooth muscle [Ca2+]i in the porcine coronary artery. 7. CGRP (8-37) significantly antagonized the relaxant effects of adrenomedullin and alpha-CGRP in the porcine coronary artery. However, it had little effect on the relaxations induced by the beta-isoform of CGRP (beta-CGRP). 8. These results suggest that in the rat aorta, adrenomedullin and alpha-CGRP increase the endothelial [Ca2+]i, activate nitric oxide synthase and release nitric oxide, without a direct inhibitory action on smooth muscle. In the porcine coronary artery, in contrast, adrenomedullin and alpha-CGRP directly act on smooth muscle, increase cyclic AMP content, decrease the smooth muscle [Ca2+]i and inhibit contraction. The rat aortic endothelium seems to express the CGRP receptor which is sensitive to alpha-CGRP, beta-CGRP and CGRP (8-37) and the adrenomedullin specific receptor. The porcine coronary smooth muscle, in contrast, seems to express two types of CGRP receptor; one of which is sensitive to alpha-CGRP, CGRP (8-37) and adrenomedullin and the other is sensitive only to beta-CGRP.     

A construction algorithm for designing guide paths of automated guided vehicle systems

A construction algorithm is suggested to design guide path networks for automated guided vehicle systems (AGVSs). This study uses the total travel time, including waiting and interference time, of vehicles as the decision criteria for determining the direction of path segments on unidirectional guide path layouts. The Q-learning technique is applied to estimate the travel times of vehicles on path segments. Computational experiments were performed to evaluate the performance of the proposed algorithm. The simulation results showed that the proposed algorithm is superior to Kim & Tanchoco's (1993) algorithm in terms of the average travel time, the interference time and the number of deliveries.     

Enhanced enzyme activity and enantioselectivity of lipases in organic solvents by crown ethers and cyclodextrins

Lipases from Candida rugosa (CRL) and Pseudomonas cepacia (PCL) were co-lyophilized with cyclic oligoethers including four crown ethers and nine cyclodextrins (CyDs), and their transesterification activity and enantioselectivity in organic solvents were evaluated. The PCL co-lyophilized with each additive showed simultaneously enhanced enzyme activity and enantioselectivity when compared to the native lipase lyophilized from buffer alone; in contrast, such enhancement was not observed for the co-lyophilized CRL. Among the cyclic oligoethers examined, permethylated betaCyD (Me1.78betaCyD), as the most suitable additive, was used for the optimization of both the co-lyophilized PCL preparation and reaction conditions by determining the effects of varying the additive/lipase ratio, aqueous pH, the nature of organic solvents, and temperature. The initial rate determined for the transesterification between racemic 2,2-dimethyl-1,3-dioxolane-4-methanol and vinyl butyrate in diisopropyl ether at 30 degrees C increased by up to 17-fold and the enantioselectivity represented by E could be doubled. While there was an inverse correlation between temperature and enantioselectivity, with the Me1.78betaCyD-PCL co-lyophilizate, the reaction rate even at 0 degrees C was much higher than that at higher temperatures in the native PCL-catalyzed reaction. Hence, this method seems to be of practical use for the large-scale production of optically active compounds.