Synthesis of new azino fused benzimidazolium salts. a new family of DNA intercalating agents. I

A series of new pyrido[1,2-a]- and pyridazino[1,6-a]benzimidazolium salts have been synthesized from readily available 1,3-disubstituted 2-alkylbenzimidazolium salts. Their affinity to DNA and in vitro cytotoxicity versus HT-29 have been tested. The initial results show that the title compounds are a new family of intercalating agents.     

"Pink urine" in morbidly obese patients following gastric partitioning.

A pink coating on the inner surface of plastic urinary tubing, which gave the impression that the urine was pink, had frequently been noted 4 to 24 hours following gastric partitioning by means of a stapler in morbidly obese patients. A study was therefore done in 187 such patients as well as in 14 patients of normal weight who had undergone abdominal surgery of comparable magnitude. Postoperatively "pink urine" was observed in 32% of the obese patients but in none of the nonobese patients; however, a pink sediment remained following centrifugation of urine collected postoperatively from all the obese patients. Microscopy of this sediment showed crystals of uric acid dihydrate; these were infrequent in the preoperative specimens but present in high concentration in the postoperative specimens, particularly those of "pink urine". X-ray diffraction analysis confirmed the nature of the crystals. Preoperatively the obese patients had high-normal serum levels of uric acid. Postoperatively in all the groups of patients the serum levels of uric acid decreased while the urine levels and the urinary clearance of uric acid increased; the last two values, however, were significantly greater, both preoperatively and postoperatively, in those who were morbidly obese. Compared with the patients who did not have "pink urine" the patients with "pink urine" were significantly more obese and had a significantly lower postoperative urine pH. The latter also had a marked postoperative increase in urine osmolality and were the only patients to have a significant postoperative decrease in urine output. Thus, the pink colour of this group''s urine was attributed to precipitation of uric acid crystals, fostered by a decrease in pH and an increase in concentration of the urine.     

Serological analysis and pathogenic potentials of Wangiella dermatitidis isolated from bats

Methods for the preparation of antigens from clinically isolated cultures of Aspergillus were standardized. Sera from 25 suspected cases of pulmonary aspergillosis were tested against antigens prepared by us, from 4 strains of A. fumigatus and one strain of A. flavus, using the Ouchterlony double diffusion and immunoelectrophoretic techniques.Of the 25 sera tested, 18 reacted positively with antigens of A. fumigatus, one with A. flavus and 2 with both these species. Antigens of two non-pathogenic Aspergilli included in the study failed to react with any of the sera. Our antigen preparations gave more numerous as well as sharper precipitin lines than the commercial Bencard antigens which were used for comparison. Moreover, mycelial antigens from 48 to 96 h old cultures revealed precipitin lines comparable to that of the routine, 4 week old culture filtrate antigens, thus suggesting that the incubation period for obtaining antigens could be cut down considerably.Memoir No. 323 from the Centre of Advanced Study in Botany.Deceased     

On the frequency of isothermal germination in seeds of Dolichos biflorus L.

The relative frequencies of seed germination show positivelyskewed distributions along the time of isothermal incubation.Unimodal patterns prevailing between 19.3? and 31.4?C changeinto progressively polymodal distributions both below 19.3?and above 31.4?C. None of the distributions fit the adjustedgaussians, except at 8.0? and at 40.6?C. (Received September 29, 1977; )     

Toad bladder amiloride-sensitive channels reconstituted into planar lipid bilayers

In the present study we used established methods to obtain apical membrane vesicles from the toad urinary bladder and incorporated these membrane fragments to solvent-free planar lipid bilayer membranes. This resulted in the appearance of a macroscopic conductance highly sensitive to the diuretic amiloride added to the cis side. The blockage is voltage dependent and well described by a model which assumes that the drug binds to sites in the channel lumen. This binding site is localized at about 15% of the electric field across the membrane. The apparent inhibition constant (K(0)) is equal to 0.98 microM. Ca2+, in the micromolar range on the cis side, is a potent blocker of this conductance. The effect of the divalent has a complex voltage dependence and is modulated by pH. At the unitary level we have found two distinct amiloride-blockable channels with conductances of 160 pS (more frequent) and 120 pS. In the absence of the drug the mean open time is around 0.5 sec for both channels and is not dependent on voltage. The channels are cation selective (PNa/PCl = 15) and poorly discriminate between Na+ and K+ (PNa/PK = 2). Amiloride decreases the lifetime in the open state of both channels and also the conductance of the 160-pS channel.     

Ascorbate oxidase from Cucurbita maxima

Ascorbate oxidase is present in homogenates of the flesh of Cucurbita maxima fruits. Its activity is independent of ascorbate concentration over th     

Gene expression in normal and virally transformed mouse 3T3B and hamster BHK21 cells

Cell lines 3T3B (mouse), 3T3B-SV40, BHK21 (hamster) and BHK21 polyoma virus (PyY) were labelled with [³⁵S]methionine under conditions in which 500–600 cpm were incorporated per cell during a 20 h incubation period. Two-dimensional gel electrophoresis analysis of the total [³⁵S]methionine-labelled polypeptides from 200–300 cells followed by fluorography revealed about 500 acidic (isoelectric focusing, IEF) and 150 basic polypeptides (non-equilibrium pH gradient electrophoresis, NEPHGE) whose position could be reproducibly assessed. Counting of 33 abundant acidic polypeptides present in both 3T3B and 3T3B-SV40 revealed significant changes in the relative proportion of ten of them. Seven, including the subunit of the 100 Å filaments ‘fibroblast type’ (55K) (1.1% in 3T3B; 0.6% in 3T3B-SV40), three cytoarchitectural proteins and three soluble proteins, corresponded to a decrease of 40% or more in the radioactivity of the spots in transformed cells, and only in three cases was there a significant increase in radioactivity of polypeptides in 3T3B-SV40 cells. Among the polypeptides that show less than 40% variation we have identified total actin (42K) (13% of total label in 3T3B; 10% in 3T3B-SV40), α- and β-tubulin (55K) (1.6% of total label in 3T3B; 2% in 3T3B-SV40), eleven polypeptides present in Triton skeletons, and nine soluble proteins. We have also observed 25 obvious changes in polypeptide intensities (16 acidic and 9 basic) but these were not quantitated. Only three polypeptides were found in transformed cells that were not detected in normal cells. One of these corresponded to the large T antigen and the other two to Triton-soluble proteins of a molecular weight in the range of 52–54K. Similar quantitative studies on the hamster BHK21/BHK21PyY pair confirmed at least the major observations made in 3T3B and 3T3B-SV40.     

Alcohol:NAD oxidoreductase in brain of rats from a colony fed dilute ethanol for many generations.

—Alcohol:NAD oxidoreductase (EC 1.1.1.1) was studied in brain cortex, hypothalamus, cerebellum and midbrain of adult and immature rats, and in the whole encephalon of neonatal rats. The rats used in this study were (i) from a colony which has been given 12% (v/v) aqueous ethanol as the only fluid for 54 generations (‘E.F.’ rats); (ii) rats removed from this colony after the forty-eighth generation and thereafter fed water instead of the alcohol solution (‘E.F./H₂O’ rats); and (iii) normal rats. Enzyme activity in the 20,000 g supernatant of tissue homogenates was measured by the method of Raskin and Sokoloff. Activity was found to be highest in neonatal rat brain and to decrease as the age increased. Activity in the hypothalamus of adult E.F. rats was significantly higher than that found in the same region of adult E.F./H₂O rats. Immature rat cerebellum alcohol:NAD oxidoreductase activity was higher both in ‘E.F.’ and ‘E.F./H₂O’ suggesting a possible genetic change be involved in this CNS region. It may be concluded that, with the exception of neonatal rats, ethanol consumption induces an increase in rat CNS alcohol :NAD oxidoreductase activity.     

Vegetative innervation of the esophagus. II. Intraganglionic laminar endings.

The intraganglionic laminar endings in the esophagus of the cat and the rhesus monkey show absolute equivalence between the results in both species from the morphological standpoint. The different types of apparatus found are described, with their location in the esophagus and their percentage distribution in relation to the different portions of its wall. The osmium tetroxide-zinc iodide technique gives pictures equivalent to those using silver impregnations, with the added advantage that the former brings out the morphological details more clearly, to the point of showing up the peculiar characteristics of the edges with their thorn-like protrusions. The complete independence of these structures within the ganglion is confirmed, and evidence is provided for rejecting the possibility that they might be dendritic prolongations of the neuronal elements composing the intramural ganglia. A possible afferent function is proposed, which, however, must be considered an open question, pending the results of further experimental investigation.