Application of CNDO2 theoretical calculations to interpretation of the chemical reactivity and biological activity of the syn and anti diolepoxides of benzo[a]pyrene

$\text{CNDO}\text{2}$ molecular orbital theoretical calculations performed on the anti and syn diolepoxides (1 and 2) of the potent carcinogen benzo[a]pyrene provide insight into the molecular structure and reactivity of these mutagenic and carcinogenic hydrocarbon metabolites. Hydrogen-bonded interaction between the 7-HO proton and the epoxide oxygen atom of 2 is shown to be absent in the normal semichair conformation of the tetrahydro ring, (H…O bond distance = 2.7 Å), but is energetically favored in a somewhat distorted puckered structure (H…O bond distance = 1.7 Å). Unexpectedly, internal H-bonding alters the relative electron density at C₉ and C₁₀, leading to prediction of the former as the more electrophilic center. Since all reactions of 2 take place exclusively at C₁₀, transannular H-bonding is concluded not to contribute significantly to the structure of 2. Diolepoxide reactions with both weak and strong nucleophiles and with DNA are discussed and the mechanisms interpreted in terms of molecular structure as determined by the theoretical calculations.     

Meningococcal Disease in California: Epidemiology and Management

Between 1969 and 1975 in California, 1,953 cases of meningococcal disease were reported. For cases reported in 1973, 1974 and 1975, detailed information about chemoprophylaxis of cases and contacts was obtained in addition to demographic and laboratory data. A review of data for the seven years showed a reduction in the case rate from 2.6 to 0.6 per 100,000 population, but this drop was due primarily to a very substantial decline in the military rate from 35.7 to 1.8 per 100,000 population. No reduction was apparent in the case fatality rate. Five groups of associated meningococcal disease cases were identified for a total of nine secondary or coprimary cases among 862 household contacts. Associated cases occurred in 10.4 per 1,000 household contacts—a rate several hundred times greater than that for the general population.The study findings indicate that many physicians are unaware of the following: (1) nonhousehold contacts are at little or no risk of contracting meningococcal disease; (2) prophylaxis should be offered only to household or intimate contacts immediately upon identification of an index case without waiting for test results for meningococcal carriage; (3) valid medical and epidemiologic indications exist for administering prophylaxis to household contacts who are culture negative as well as those who are culture positive; (4) the current drug of choice for prophylaxis is rifampin, but since no drug is completely effective, close medical observation remains the most important factor in the management of household or intimate contacts to meningococcal disease.     

Studies of the diphtheria toxin receptor on chinese hamster cells

Concanavalin A, wheat germ agglutinin and the ovalbumin glycopeptide are all inhibitors of the cytotoxic effect of diphtheria toxin on Chinese hamster cells. Ovalbumin glycopeptide loses its inhibitory property after treatment with β-N-acetylglucosaminidase. This demonstrates the importance of the glycopeptide structure for the mechanism of inhibition. The glycopeptide may be a toxin cell-surface receptor analogue. Diphtheria toxin-resistant mutants were isolated in order to search for cells that might have an altered toxin receptor. One mutant was 10-to 15-fold more resistant to diphtheria toxin than wild-type cells when protein synthesis was measured as a function of toxin concentration. However, when protein synthesis was measured as a function of time at a high toxin concentration, the time before onset of inhibition was identical in the mutant and wild-type cells. We present evidence indicating that the resistance of this mutant can be accounted for by a decreased affinity of toxin for a cell-surface receptor.     

The biogeography of Lessoniaceae,with special reference to Macrocystis C. Agardh (Phaeophyta: Laminariales)

The bipolar distributions of Lessoniaceae and Macrocystis have been explained by migration out of a ‘centre of origin’ and across the tropics by means of dispersal, but controversy centres on the issue: which sector is the true centre of origin? We provide biological, palaeo-oceanographic and geological evidence that leads us to reject the centre of origin/migration theory and methodology in explaining ‘bipolarity’. As an alternative, a process of vicariant differentiation out of a Pacific Ocean/Southern Ocean ancestral complex is proposed. Moreover the biogeographic relationship between the southwest and northeast Pacific is shown to be a general phenomenon and not restricted to marine algae.     

人源性流行性出血热病毒的形态特征

本文报道流行性出血热病毒(汉坦病毒)H-114株的电镜形态。发现形态发生以内质网膜和胞浆膜芽生为主。病毒颗粒为圆形或卵圆形。具有双层膜结构,大小为90～120nm。提出了汉坦病毒形态发生的理论观点。     

Expression of dihydropyridine-sensitive brain calcium channels in the rat central nervous system.

We have localized dihydropyridine (DHP-sensitive calcium channels in rat brain by in situ hybridization and immunohistochemistry. The mRNA for the dihydropyridine-sensitive calcium channel alpha 1 subunit (DHPR-B) is prominently localized in neuronal cells in the olfactory bulb, dentate gyrus, hippocampus, arcuate nucleus, paraventricular nucleus, ventromedial nucleus, cerebral cortex, superior colliculus and the cerebellar Purkinje cell layer. Strong expression of DHPR-B mRNA was also found in the pituitary and pineal glands. DHP-sensitive calcium channel alpha 1 subunit distribution has also been examined immunohistochemically with polyclonal antibodies raised against synthetic peptides specific for the DHPR-B alpha 1 subunit protein. The results from immunohistochemistry were in good agreement with those from in situ hybridization. Thus, regional distribution and localization of DHPR-B mRNA and alpha 1 subunit protein in rat brain suggest that this type of DHP-sensitive brain calcium channel may play an important role in excitation-secretion coupling functions in the neuroendocrine system.     

Carbohydrate specificity of the receptor sites of mistletoe toxic lectin-I.

The carbohydrate specificity of mistletoe toxic lectin-I (ML-I) was studied by haemagglutination-inhibition assay. The results indicated that ML-I has a broad range of affinity for Gal alpha,beta linked sequences. The galabiose (E, Gal alpha 1----4Gal) sequence, a receptor of the uropathogenic E. coli ligand, was one of the best disaccharide inhibitors tested. The lectin also exhibits affinity for Lac(Gal beta 1----4Glc), T(Gal beta 1----3GalNAc), I/II(Gal beta 1----3/4GlcNAc) and B(Gal alpha 1----3Gal) sequences. Gal alpha 1----4Gal and Gal beta 1----4Glc are frequently occurring sequences of many glycosphingolipids located at the mammalian cell membranes, such as intestinal and red blood cell membranes, for ligand binding and toxin attachment. This finding provides important information concerning the possible mechanism of intoxication of cells by the mistletoe preparation.