In Vitro and In Vivo Laboratory Evaluation of Cephaloglycin and Cephaloridine

Two new antibiotics, structurally related to cephalothin, have been given the generic names cephaloglycin and cephaloridine. Cephaloglycin is the dipolar ion of 7-(d-α-aminophenylacetamido)-cephalosporanic acid. Cephaloridine is 7-[α-(2-thiophene)acetamido]-3-(1-pyridylmethyl)-3-cephem-4-carboxylic acid betaine. These new compounds were evaluated simultaneously. The broad spectrum of activity observed in vitro and in vivo with both antibiotics, the good oral absorption obtained with cephaloglycin, and the stability of cephaloridine are emphasized. The data suggest that both antibiotics merit clinical trial in humans.     

Effects of various fixatives on the reactivity of plant cell tubulin and calmodulin in immunofluorescence microscopy

Summary We have examined the suitability of a variety of fixation regimes for immunofluorescence localization of tubulin and calmodulin in meristematic plant cells. Acrolein and most fixatives that contain glutaraldehyde (GA), while they have been employed by others in immunoenzyme, immunogold or immunofluorescence studies of plant endosperm, animal or plant tissue culture cells, cause unacceptably high background fluorescence of the dense cytoplasm of root meristem cells. Bifunctional imidoester and carbodiimide reagents do not give satisfactory results, either. Fixatives that have produced good results include paraformaldehyde (PFA) with the addition of picric acid or zinc salts or at high pH, a combination of PFA/GA/picric acid, and prefixation in PFA plus a monofunctional imidoester followed by PFA/GA. All of these cross-link the cytoplasm well enough so that cells can withstand isolation procedures, preserve antigenicity, allow antibody penetration and provide good contrast between specific and background fluorescence. The last two fixatives are of particular interest because of the potential they offer for immunoelectron microscopy of densely cytoplasmic, walled cells from tissues.     

Cisplatin Chronotherapy and Disulfiram Rescue Reduce Toxicity without Interfering with Anticancer Activity: Animal Findings and Preliminary Clinical Experiences

Cisplatin-induced mortality and nephrotoxicity are each predictably worse when the drug is given at certain points within the circadian schedule. Oral disulfiram protects rats from toxic effects at some circadian stages but not others. This manuever does not diminish the anticancer activity of cisplatin in these rats. Human beings given 2 g of oral disulfiram and high doses of cisplatin at the circadian stage associated with least cisplatin nephrotoxicity (prospectively determined potassium excretion acrophase) suffer little or no kidney damage. Disulfiram administration apparently does not interfere with the antineoplastic activity of cisplatin in humans. This is the first demonstration of the feasibility of assignment of treatment time according to a measure of the patient's 'internal clock' as assessed by pretreatment marker rhythmometry. It also establishes the feasibility of giving disulfiram to human beings.     

Diminished glucocorticoid tonus in obese strain (OS) chickens with spontaneous autoimmune thyroiditis: increased plasma levels of a physicochemically unaltered corticosteroid-binding globulin but normal total corticosterone plasma concentration and normal glucocorticoid receptor contents in lymphoid tissues

Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT) display several signs of a general immune dysbalance, some of which may be related to altered endocrine mechanisms such as the glucocorticoid tonus. The latter is the combined result of corticosterone (CN) production, metabolism as well as excretion, and the binding of CN to corticosteroid binding globulin (CBG) and glucocorticoid receptors (GR). The present study deals with the comparative investigation of these parameters in OS and normal White Leghorn (NWL) chickens. The results obtained with radioimmunoassay for CN and radioligand saturation assays for plasma CBG as well as GR in the thymus were as follows: (1) both OS and NWL have equal total CN levels; (2) however, OS chickens exhibit elevated CBG levels, whereas the physicochemical parameters (equilibrium affinity, specificity spectrum) of CBG were equal in OS and NWL; (3) the GR capacities and affinities were equal in both OS and NWL throughout development until thymic involution. Similarly, the specificity, affinity, and sedimentation behaviour were equal in OS and NWL. (4) Furthermore, no differences were found in the response of OS and NWL splenocytes to the suppressive effect of glucocorticoids in vitro, also excluding postreceptor alterations at the cellular level in the OS. From these findings we conclude that the increased CBG levels, which are not compensated for by either increased CN plasma levels or by increased receptor capacities or affinities in lymphatic organs, represent a diminished glucocorticoid tonus in OS chickens. This may have immunoregulatory consequences which, in turn, may contribute to the development of SAT.     

Immunofluorescence microscopy of tubulin and microtubule arrays in plant cells. II. Transition between the pre-prophase band and the mitotic spindle

Summary Changing patterns of tubulin immunofluorescence as onion root meristematic cells progress from a mature pre-prophase band (PPB) stage into mitosis are reported here. The PPB reaches its narrowest profile at maturity and then remains the same width throughout the rest of the transition. Concomitant with continuation of chromatin condensation and nucleolar breakdown, both initiated earlier in pre-prophase, alignment of fluorescent fibers along the nuclear envelope (NE) changes. Perinuclear microtubules (MTs), which were parallel to the PPB or randomly arranged when first seen at earlier stages of pre-prophase, assume the orientation of spindle MTS at late preprophase. They lie close to the NE and follow the nuclear contour, ultimately converging upon two focal points directly at the NE surface. MTs also can be seen traversing the cytoplasm between nucleus and cell periphery.As spindle initiation proceeds, PPB fluorescence intensity decreases and eventually is exceeded by the NE-associated fluorescence. PPB and spindle arrays co-exist briefly in the transition period, with spindle MTs typically aligned perpendicular to both the axis of the PPB and its constituent MTs. Total disappearance of the PPB occurs only after chromosome condensation is complete and the nucleus is contained within a spherical or ellipsoid cage of fluorescent fibers comprised of two non-overlapping half-spindles. Like the fully formed prophase spindle which follows, the incipient spindle is neither barrel-shaped nor fusiform, but rather displays MTs radiating from the poles in a smooth arc.     

Continuous fermentation in slant tubes

Continuous, steady-state grape-juice fermentation, carried out in experimental slant-tube fermentors, was characterized by complete fermentation, even at fast pumping rates, because efficient cell retention, as well as rapid yeast growth, quickly built cell density up to the limit permitted by the juice supply rate. Essentially complete fermentation was easily achieved with a juice residence time of 3.1 hr, compared to about 120 hr in normal batch fermentation. Successful continuous fermentation required constancy of gas and liquid flow through the tubes, placing some restrictions on choice of tube configurations. The validity of design equations, developed previously from a settling model, was tested, and some practical aspects of their application to fermentor design and operation were demonstrated.