Thymidylate synthase is localized to the nuclear periphery in the yeast Saccharomyces cerevisiae

To date, the organization of DNA precursor synthesis within eukaryotic cells remains unresolved. Previous studies have suggested the existence of a multienzyme complex that is responsible for DNA precursor synthesis and is associated with sites of replication within the nucleus. Contrasting this, other studies have proposed that DNA precursor synthesis occurs outside the nucleus. To further these studies, we have addressed the location where thymidylate synthase resides in yeast. Subcellular fractionation experiments indicate thymidylate synthase is associated with purified nuclei. Consistent with this, immunofluorescence analysis suggests that thymidylate synthase is situated at the nuclear periphery.     

Metabolic activation and carcinogen-DNA adduct detection in human larynx

Putative carcinogen-DNA adducts in human larynx tissues (n = 25) from smoker and non/ex-smoker patients were examined by 32P-postlabeling and compared with the metabolic activation capacity of larynx microsomes and cytosols from the same tissues. Hydrophobic DNA adducts were evident only in smokers, and chromatographic profiles of the adducts were similar using either the butanol extraction or nuclease P1 enhancement method, which suggested that the adducts may be derived from polycyclic aromatic hydrocarbons but not aromatic amines. Immunoblots of larynx microsomes using anti-cytochrome P450 1A1/1A2, 2C, 3A4, 2E1, and 2A6 antibodies showed intensities ranging from 1-10% of that typically observed with human liver microsomes. Enzymatic assays of larynx microsomes showed appreciable activity for benzo(a)pyrene hydroxylation (P450 1A1 and 2C) but not for 4-aminobiphenyl N-oxidation (P450 1A2), which indicated that the observed immunoreactivity was for P450 1A1; this represents the highest level of this P450 yet detected in human extrahepatic tissues. Accordingly, total DNA adduct levels in the larynx correlated strongly with levels of P450 2C, 1A1, and 3A4 but not with P450 2E1 or 2A6. Larynx cytosols also showed appreciable aromatic amine N-acetyl-transferase activity for p-aminobenzoic acid (NAT-1) but not for sulfamethazine (NAT-2); however, NAT-1 activity was not correlated with total DNA adducts, which is again consistent with the lack of aromatic amine-DNA adducts detected by 32P-postlabeling. Thus, these results suggest that the DNA adducts detected in human larynx are largely derived from metabolic activation of polycyclic aromatic hydrocarbons in cigarette smoke by P450 2C, 3A4, and/or 1A1.     

Haemodynamic changes in portal hypertension: new insights in the pathogenesis and clinical implications

In man and experimental animals, portal hypertension with portal-venous collaterals, is associated with a hyperdynamic circulation, caused by peripheral vasodilatation, mainly in the splanchnic bed. This peripheral vasodilatation is clinically important, since it is thought to be responsible for the pathogenesis of complications of portal hypertension such as ascites, the hepatorenal syndrome and portal hypertensive gastropathy and colopathy. Many cirrhotic patients may not die primarily because of their hepatic dysfunction, but rather because of the consequences of the circulatory abnormalities which are secondary to the liver disease. Circulating hormonal vasodilators from intestinal origin such as glucagon, insufficiently cleared by the liver, are only partly responsible for these changes. Recent experimental data point to a role for an increased production of the locally acting potent vasodilator nitric oxide in the vascular wall, in the pathogenesis of the hyperdynamic circulation. Furthermore, nitric oxide seems to play an important role in the development of portal-venous collaterals. Modulation of the nitric oxide production might offer therapeutic options for the treatment of portal hypertension and its complications.     

The effect of nerve injury on the incidence and distribution of branched pulpal axons in the ferret

In a previous electrophysiological study in ferrets, we demonstrated that some axons in the inferior alveolar nerve branch to supply the pulps of two teeth. We have now investigated the incidence and distribution of branched pulpal axons at various intervals after nerve injury and subsequent regeneration, to study the extent to which the innervation of the teeth returns to normal. In adult male ferrets under anesthesia, the left inferior alveolar nerve was either sectioned (31 animals) or crushed (10 animals). Following recovery periods of six weeks, three months, or one year after nerve section and three months after nerve crush, electrophysiological recordings were made by insertion of pairs of Ag/AgCl electrodes into cavities cut into left mandibular teeth. Electrical stimuli were applied to each tooth in turn, and averaged responses were recorded individually from the other teeth. Latency and amplitude of the action potentials were used to characterize responses from branched pulpal axons. For some branched units, the point of branching was established by determination of the site of the inferior alveolar nerve section which abolished the response. When compared with controls, the results indicated that, following short recovery periods after nerve section, there was an increase in the number of branched pulpal axons supplying non adjacent teeth, and this branching had occurred at the initial site of nerve injury. Following long recovery periods, there were fewer branched axons than at earlier stages of recovery, but this apparent remodeling had not selectively eliminated axons which branched at the injury site to supply widely separated targets. Nerve crush injury resulted in no increase in the incidence of branched pulpal axons, and branching at the injury site was rare.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reaffirming professionalism through the education community

OBJECTIVE: To determine the role of the clinical training environment and a medical education community in reaffirming medical professionalism among physicians-in-training and faculty. DATA SOURCES: Published articles on undergraduate and graduate medical education and sociology works on professionalism were identified through research. STUDY SELECTION: Studies were selected that illustrated barriers to professionalism in medical education and patient care and the professional conduct of medical students, residents, and faculty. RESULTS: Factors that undermined the medical education community were the specialization of medicine, the faculty reward systems, and the service demands of residency because of the economics of health care. CONCLUSIONS: Establishment of a firm system with a core teaching faculty, creation of mentoring and role modeling programs, implementation of a longitudinal curriculum on medical professionalism, evaluation of physicians on professional conduct, and evaluation of the clinical training environment are suggested as strategies to re-establish an education community and reaffirm professionalism in medicine.     

美国"精明增长"的策略、案例及在中国应用的思考

要将美国“精明增长”应用到中国就必须考虑中国特有的工业化、城市化背景。本文介绍了“精明增长”的有关策略及在美国较为成功的案例,提出在中国应用“精明增长”的一些思考。     

Inhibition of pink color development in cooked, uncured ground turkey through the binding of non-pink generating ligands to muscle pigments

The pink color defect in cooked, uncured turkey is a sporadic problem that can result in economic loss and consumer dissatisfaction. Fourteen ligands were tested in ground turkey samples for their ability to reduce pink color development in control samples and in the presence of 150 ppm sodium nitrite or 1.0% nicotinamide (pink color producing agents). The 14 ligands evaluated were: 3-amino pyridine (AP), 4-benzoylpyridine (BP), diethylenetriamine pentaacetic acid (DA), ethylenedinitrilo-tetraacetic acid disodium salt (EA), 2,3 dihydroxybenzoic acid (DB), 3-ethyl pyridine (EP), trans 1,2-diaminocyclohexane-N,N,N',N' tetraacetic acid monohydrate (HA), calcium reduced nonfat dried milk (NM), 2,3 phthalic acid (PA), 3-picoline (PC), pyrrole (PY), pyridazine (PZ), pyridinedicarboxcylic acid (YA), and pyrazinedicarboxcylic acid (ZA). All ligands were incorporated into ground turkey at 0.20 mg/g (meat weight basis) except for NM (30 mg/g). Color was evaluated using a reflectance spectrophotometer to measure pigment changes (nicotinamide hemochrome, nitrosohemochrome) and with a chroma meter to determine CIE L* a* b* values. Reduction in pink color development was apparent with the addition of the ligand alone and in the presence of sodium nitrite and especially nicotinamide. The four most effective ligands tested were DA, EA, HA, and NM. In general, pink color reduction was highest in the ligand only and the ligand plus nicotinamide samples as was observed by CIE a* and nicotinamide hemochrome value reductions.     

Pulmonary and allergy subspecialty care in adults with asthma. Treatment, use of services, and health outcomes

This study examined the relationship of several maternal variables to the duration of exclusive breast-feeding and the total duration of breast-feeding, along with attitudes, perceptions, and beliefs about breast-feeding among women living in poor neighborhoods of Managua, Nicaragua. The field work was carried out in December 1992 and January 1993 using qualitative and quantitative methods. A structured questionnaire was administered in interviews with 556 mothers of children under 12 months of age, and meetings of four directed discussion groups were held, in which a total of 20 women participated. At one week of age, almost all the children of the mothers who were surveyed had been breast-fed, but only 45% had been exclusively breast-fed. At 12 weeks old, 30% were already completely weaned. The discussion groups revealed the coexistence of positive opinions about both breast-feeding and bottle-feeding. However, exclusive breast-feeding was considered harmful for the mother, and breast milk was not thought to be sufficient nourishment for the child. Previous experience was strongly related to the duration of exclusive breast-feeding and to total breast-feeding duration. Attitudes, social support, and work situation were important factors influencing the total length of time women breast-fed a child. In general, the results obtained through the interviews and in the discussion groups were in agreement and showed that the elements needed to promote exclusive breast-feeding were social support, a favorable community environment, and policies that dealt with problems faced by working mothers. The complementary research methods were useful for obtaining information about the relative importance of different factors that determine the duration of breast-feeding and for understanding that practice in greater depth from the mother's point of view.