Quinine-induced agranulocytosis: toxic effect of quinine bisulphate on bone marrow cultures in vitro.

In a case of quinine-induced agranulocytosis marrow culture studies confirmed the inhibitory effect on the patient''s cells of equivalent therapeutic plasma concentrations of quinine. Similar concentrations had no effect on normal marrow cells. Quinidine, the stereoisomer of quinine, had no effect on either cells from the patient or normal cells. The results encourage the use of in-vitro bone marrow cultures for identifying drugs responsible for agranulocytosis.     

Modified xanthan—its preparation and viscosity

Xanthan with various pyruvic acid and acetate contents has been prepared from a single commercial polysaccharide sample using optimised chemical conditions (acid and alkali hydrolysis, respectively) for removal of acetal and acyl groups. The only significant change found on analysis of the modified xanthans was loss of pyruvic acid and/or acetate; no low moleculur weight carbohydrate-containing material was released. Contrary to some previous reports, evidence is presented to show that the pyruvic acid acetal and o-acetyl contents of xanthan do not affect solution viscosity. The viscosities of native, pyruvate-free and pyruvate/acetate-free xanthan solutions (0·3% w/v) were similar at shear rates 8·8–88·3 s^?1 in both distilled water and 1% KCl. Over the concentration range 0·2-1·5%, the viscosities of native and pyruvate-free xanthan at 10 s^?1 were similar. The viscosity increase on addition of 1% KCl to salt-free xanthan solutions was independent of pyruvic acid acetal substitution. Our results suggest that xanthan samples with various pyruvic acid acetal and o-acetal contents, prepared under different fermentation conditions of Xanthomonas campestri should not normally be used for assessing the contribution of these groups to solution viscosity.     

In vivo binding and clearance of circulating antigen by bispecific heteropolymer-mediated binding to primate erythrocyte complement receptor.

We have used the avidin/biotin system to construct soluble, cross-linked bispecific heteropolymers containing mAb to both the primate E C receptor and the DNP group. These heteropolymers facilitate in vitro binding of DNP-bovine gamma-globulin (DNP-BGG) to both human and squirrel monkey E. Intravenous injection in squirrel monkeys of DNP-BGG followed by heteropolymer leads to E binding and clearance from the circulation of a significant fraction of both heteropolymer and DNP-BGG, without lysis or clearance of the E. This methodology may potentially be used to treat a variety of infectious diseases and other syndromes associated with blood-borne pathogens.     

Metabolism of phenanthrene by Phanerochaete chrysosporium.

The white rot fungus Phanerochaete chrysosporium metabolized phenanthrene when it was grown for 7 days at 37 degrees C in a medium containing malt extract, D-glucose, D-maltose, yeast extract, and Tween 80. After cultures were grown with [9-14C]phenanthrene, radioactive metabolites were extracted from the medium with ethyl acetate, separated by high-performance liquid chromatography, and detected by liquid scintillation counting. Metabolites from cultures grown with unlabeled phenanthrene were identified as phenanthrene trans-9,10-dihydrodiol, phenanthrene trans-3,4-dihydrodiol, 9-phenanthrol, 3-phenanthrol, 4-phenanthrol, and the novel conjugate 9-phenanthryl beta-D-glucopyranoside. Identification of the compounds was based on their UV absorption, mass, and nuclear magnetic resonance spectra. Since lignin peroxidase was not detected in the culture medium, these results suggest the involvement of monooxygenase and epoxide hydrolase activity in the initial oxidation and hydration of phenanthrene by P. chrysosporium.     

DNA-dependent adenosinetriphosphatase A is the eukaryotic analogue of the bacteriophage T4 gene 44 protein: immunological identity of DNA replication-associated ATPases.

We report the construction of three stable murine hybridomas that secrete monoclonal antibodies which recognize calf thymus DNA-dependent adenosinetriphosphatase A. All three of the antibodies react specifically with calf thymus ATPase A and the gene 44 protein from the bacteriophage T4 DNA-dependent ATPase. Each of the three anti-ATPase A antibodies appears to recognize a different epitope and none of the antibodies inhibit DNA-dependent ATP hydrolysis by ATPase A. Furthermore, one of the antibodies has been shown to react with two different preparations of HeLa cell DNA-dependent ATPases and a yeast DNA-dependent ATPase, all of which have been implicated in the enzymology of DNA replication. These findings provide strong evidence for the role of ATPase A in DNA replication. These observations lead us to conclude that, apart from the nucleotide binding sites, there are at least three epitopes common to both the bacteriophage and eukaryotic DNA-dependent ATPases that we have examined and that the different preparations of the eukaryotic ATPases contain the same DNA-dependent ATPase.     

Scaling of limb joint surface areas in anthropoid primates and other mammals

Recently it was reported that limb joint surface areas scale positively allometrically with body weight in anthropoid primates. This was attributed to the biomechanics of weight bearing: larger animals must require relatively larger joint surfaces to withstand relatively greater weight-related stresses on the joints. Our data on humeral and femoral geometry and joint surface areas in 73 species belonging to six mammalian orders (including primates) demonstrate that positive allometry of joint surface areas is not a general phenomenon for mammals and cannot have its basis among Anthropoidea in the biomechanics of weight bearing. We argue that, to the extent that positive allometric scaling of joint surface areas occurs in anthropoid primates, it is an artifact of differences in positional behaviour among distinct taxonomic groups that also happen to differ widely in body weight. Furthermore, we argue that, among mammals ranging in body size from sportive lemurs to giant pandas, functionally similar groups tend to exhibit: (1) linear dimensions (especially diameters and shaft circumferences) that scale in direct proportion to each other; and (2) joint surface areas that scale in direct proportion to the squares of linear dimensions and to the 2/3 power of body mass. In other words, limb bones of functionally similar animals fit the theoretical model of geometric similarity (or skeletal isometry). Differences in relative sizes of joint surface areas are related to differences in force transmission and movement potential among functionally distinct groups of animals.     

Detoxification of polycyclic aromatic hydrocarbons by fungi

Summary The polycyclic aromatic hydrocarbons (PAHs) are a group of hazardous environmental pollutants, many of which are acutely toxic, mutagenic, or carcinogenic. A diverse group of fungi, includingAspergillus ochraceus, Cunninghamella elegans, Phanerochaete chrysosporium, Saccharomyces cerevisiae, andSyncephalastrum racemosum, have the ability to oxidize PAHs. The PAHs anthracene, benz[a]anthracene, benzo[a]pyrene, fluoranthene, fluorene, naphthalene, phenanthrene, and pyrene, as well as several methyl-, nitro-, and fluoro-substituted PAHs, are metabolized by one or more of these fungi. Unsubstituted PAHs are oxidized initially to arene oxides,trans-dihydrodiols, phenols, quinones, and tetralones. Phenols andtrans-dihydrodiols may be further metabolized, and thus detoxified, by conjugation with sulfate, glucuronic acid, glucose, or xylose. Although dihydrodiol epoxides and other mutagenic and carcinogenic compounds have been detected as minor fungal metabolites of a few PAHs, most transformations performed by fungi reduce the mutagenicity and thus detoxify the PAHs.     

The vacuum UV CD bands of repeating DNA sequences are dependent on sequence and conformation

CD spectra were obtained for eight synthetic double-stranded DNA polymers down to at least 175 nm in the vacuum uv. Three sets of sequence isomers were studied: (a) poly[d(A-C).d(G-T)] and poly[d(A-G).d(C-T)], (b) poly[d(A-C-C).d(G-G-T)] and poly[d(A-C-G).d(C-G-T)], and (c) poly[d(A).d(T)], poly[d(A-T).d(A-T)], poly[d(A-A-T).d(A-T-T)], and poly[d(A-A-T-T).d(A-A-T-T)]. There were significant differences in the CD spectra at short wavelengths among each set of sequence isomers. The (G.C)-containing sequences had the largest vacuum uv bands, which were positive and in the wavelength range of 180-191 nm. There were no large negative bands at longer wavelengths, consistent with the polymers all being in right-handed conformations. Among the set of sequences containing only A.T base pairs, poly[d(A).d(T)] had the largest vacuum uv CD band, which was at 190 nm. This CD band was not present in the spectra of the other (A.T)-rich polymers and was absent from two first-neighbor estimations of the poly[d(A).d(T)] spectrum obtained from the other three sequences. We concluded that the sequence dependence of the vacuum uv spectra of the (A.T)-rich polymers was due in part to the fact that poly[d(A).d(T)] exists in a noncanonical B conformation.