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L Spero

Publications and source records attributed to L Spero.

At least 19 recordsLinked to original sources
PubMed1991

Further evaluation of collagen shields as a delivery system for 5-fluorouracil: histopathological observations.

Collagen shields are a potential delivery system for antifibroblast drugs such as 5-fluorouracil after filtration surgery. To determine whether collagen shields produce histologic evidence of inflammation when implanted subconjunctivally, shields were implanted into four rabbit eyes and six guinea pig eyes and retained for 7 or 14 days. Two rabbit eyes and two guinea pig eyes served as controls. Seven days after implantation in the rabbit eyes foreign-body giant cells were present at the surface of the shield, and early deposition of connective tissue was evident around the shield. The inflammatory response at 14 days was similar but more intense. In the guinea pig eyes the collagen shields induced substantially less inflammation, and there was marked shield degradation at 14 days. The results suggest that the inflammatory response in rabbits may be species specific and that collagen shields may be of value as a drug-delivery system for antifibroblast drugs in other species.

Animals↗
PubMed1987

Sequence determination and comparison of the exfoliative toxin A and toxin B genes from Staphylococcus aureus.

The DNA encoding the exfoliative toxin A gene (eta) of Staphylococcus aureus was cloned into bacteriophage lambda gt11 and subsequently into plasmid pLI50 on a 1,391-base-pair DNA fragment of the chromosome. Exfoliative toxin A is expressed in the Escherichia coli genetic background, is similar in length to the toxin purified from culture medium, and is biologically active in an animal assay. The nucleotide sequence of the DNA fragment containing the gene was determined. The protein deduced from the nucleotide sequence is a polypeptide of 280 amino acids. The mature protein is 242 amino acids. The DNA sequence of the exfoliative toxin B gene was also determined. Corrections indicate that the amino acid sequence of exfoliative toxin B is in accord with chemical sequence data.

Amino Acid Sequence↗
PubMed1985

Modulation of specific [3H]phenytoin binding by benzodiazepines.

We have shown that diazepam (ED50 2.4 microM), flunitrazepam (ED50 10.2 microM) and Ro5-4864 (ED50 5 microM) are able to enhance both total and specific [3H]phenytoin binding. Picrotoxin (IC50 1.43 microM) and chloride, either NaCl or KCl (IC50 42.4 microM) inhibit both the increase in total and specific binding of [3H]phenytoin, Ro15-1788 does not. The optimum time for this enhancement was 3-4 hours. While the ED50's for the benzodiazepines are high their order of potency suggests that an involvement of both the "peripheral type" benzodiazepine receptor and the GABA-chloride ionophore complex is likely. Clonazepam (IC50 23 microM), oxazepam (IC50 12 microM) chlordiazepoxide (IC50 35 microM) and Ro8682-10, a convulsant benzodiazepine (IC50 16 microM) all inhibit both total and specific [3H]phenytoin binding. These effects were not blocked by chloride ions, picrotoxin or Ro 15-1788, and reached equilibrium within 45 minutes. This order of potency also parallels that for the "peripheral' benzodiazepine receptor in rat brain. These data suggest the presence of a micromolar benzodiazepine receptor site which may play a role in the control of CNS excitability. Nitrazepam, medazepam, bromazepam and the tetralobenzodiazepines U38335, U42794, U43434, and U37834 had no effect on total or specific [3H]phenytoin binding nor on the actions of the other benzodiazepines described in concentrations up to 50 microM.

Animals↗
PubMed1985

Specific binding of [3H]phenytoin in the human brain.

Competition between cold phenytoin and [3H]phenytoin binding was observed in normal human brain. Binding was observed in all areas examined. The highest number of sites was in the amygdala (a total of 717.71 fmol/mg protein) and the lowest in the Brodman area (BA) 4 of the motor cortex (153.91 fmol/mg protein) and cerebellar cortex (154.4 fmol/mg protein). In three areas, amygdala, cortex area BA 38 (inferior parietal lobe), and cortex area BA 8 (premotor cortex), two sets of binding sites were observed. In these areas the Kd for the higher affinity sites ranged from 35 to 116 nM, and for the lower affinity site, from 328 to 866 nM. In the four areas where only one binding site was observed the KdS ranged from 164 to 311 nM and the Scatchard plot was linear.

Amygdala↗
PubMed1983

Enhancement of 3H-phenytoin binding by diazepam and (+)bicuculline.

3H-Phenytoin binding to the particulate fraction of rat wholebrain homogenate was studied using the filter assay technique. It was found that diazepam and (+)bicuculline methobromide caused a concentration-dependent enhancement of the total binding of 3H-phenytoin, whereas GABA and (-)bicuculline methobromide (the inactive bicuculline isomer) had no effect. In subsequent competition experiments (labelled versus unlabelled phenytoin), it was found that the presence of a potentiating concentration of diazepam transformed the biphasic phenytoin competition isotherm into a simple curve with a Hill coefficient of approximately one, and a Ki of 110 nM.

Animals↗
PubMed1983

The complete amino acid sequence of staphylococcal enterotoxin C1.

This report presents the complete amino acid sequence of staphylococcal enterotoxin C1. It has a total of 239 amino acids and a calculated Mr = 27,500. Reaction of the native toxin with trypsin produced five peptides, designated A through E. Their structures were determined after further fragmentation with cyanogen bromide, trypsin, and chymotrypsin. Overlap peptides were prepared by cleavage at the two half-cystine residues, and by the reaction of enterotoxin C1 with hydroxylamine. The latter procedure was employed when it was found that one of the three asparaginyl-glycine loci in the toxin is refractory to direct sequencing. The sequence is compared to staphylococcal enterotoxin B. Extensive homology is found, particularly in the carboxyl-terminal region. However, the segment spanned by the disulfide bond in enterotoxin C1 is three residues shorter than the corresponding segment in the B variant.

Amino Acid Sequence↗
PubMed1982

Epilepsy.

Explore the source record for details and available documents.

Anticonvulsants↗
PubMed1981

Analysis of the near-ultraviolet circular dichroic spectra of staphylococcal enterotoxins A, B and C.

The near-ultraviolet CD spectra from 260 to 300 nm of staphylococcal enterotoxins A, B and C were resolved empirically into Gaussian curves. Each spectrum contained the same six components with maximum ellipticities at virtually identical wavelengths. The rotatory strength of the bands of enterotoxin A, however, differed significantly from that of enterotoxins B and C. Each Gaussian curve was identified as corresponding to a prominent CD transition of an aromatic chromophore: two phenylalanine bands from its 1Lb transition (0-0 and 0 + 930 cm-1); four tyrosine bands from its 1Lb transition (the 800 cm-1 primary vibronic progression) with the weakest of these overlapping a phenylalanine band; and one 1Lb tryptophan band. At alkaline pH, tyrosylate CD bands arose, centered at 247-249 nm and at 295-298 nm. The intensity of the 295-298 nm bands indicated that most of the tyrosine CD in the neutral enterotoxins was contributed by buried residues. The tryptophan contribution to the CD of enterotoxin A was positive, while that of B and C was negative. Also indicative of a different milieu was the ready oxidation of the A toxin by N-bromosuccinimide and the unavailability of the single tryptophan residue in the other two toxins to this reagent. The environment of the disulfide bond was markedly diverse in the three enterotoxins. Enterotoxin C was refractory to reduction by mercaptoethanol under conditions where enterotoxins B and A were readily reduced. The contribution of the disulfide of enterotoxin B to its CD spectrum was positive with an intensity of about 9000 deg . cm2 . dmol-1 and was centered near 273 nm. The difference spectrum between native and reduced enterotoxin A was much smaller and appeared to be conformational in origin.

Circular Dichroism↗
PubMed1981

Saturable binding of [3H]phenytoin to rat brain membrane fraction.

Preliminary studies indicate that [3H]phenytoin binds in a saturable and reversible fashion to at least two distinct sites in the membrane fraction of whole rat brain. One of these displays a high affinity (Kd = 6 nM) and a low maximal capacity (Bmax = 10 pmol/g protein). The other has a low affinity (Kd = 4.8 microM) and is estimated to have a very high maximal capacity. Phenytoin binding is reduced if the membrane fraction is preincubated with proteolytic enzymes and subcellular fractionation studies indicate that P2 fraction has the largest number of binding sites. Competition experiments fail to reveal significant binding interactions with putative neurotransmitters or with other drugs except the hydantoins and anticonvulsant barbiturates. Although it is premature to speculate on the clinical significance of these findings, it is encouraging to note that the low affinity site has a Kd very similar to the therapeutic levels of phenytoin found in cerebrospinal fluid and that there seems to be some relationship between binding potency and anticonvulsant potency within the hydantoin series.

Animals↗
PubMed1980

Cross-tolerance between ethanol and morphine in the guinea-pig ileum longitudinal-muscle/myenteric-plexus preparation.

Morphinization of guinea pigs with s.c. implanted pellets (4 X 75 mg morphine base) has resulted in tolerance, within the isolated longitudinal muscle/myenteric plexus preparation, to the in vitro inhibitory effects of morphine on the electrically induced contractions, and in cross-tolerance to the inhibitory effects of ethanol. Similar results were observed with opiate-naive preparations that were incubated for 18 h in Krebs-Ringer solution containing 40 muM morphine. Daily ethanol injections (6 g/kg) resulted in tolerance to ethanol and cross-tolerance to morphine. These results suggest a commonality between ethanol and morphine actions on the myenteric plexus preparation.

Animals↗
PubMed1980

The secondary structure of staphylococcal enterotoxins A, B and C.

The circular dichroism (CD) of staphylococcal enterotoxins A, B and C was measured. The CD of enterotoxins B and C were almost identical from 250 to 320 nm, but differed from the CD of enterotoxin A. The spectrum of enterotoxin A in this wavelength region contained the same bands with respect to both location and sign, but with significant differences in intensity. The CD spectra of enterotoxins B and C were also much more alike from 190 to 250 nm. Although all three enterotoxins had a major negative extremum at 215--218 nm, its magnitude was equal in enterotoxins B and C, but was substantially decreased in enterotoxin A. The secondary structure of the enterotoxins contained little alpha-helix as analyzed with CD models. A secondary structure of entertoxin B compured from a scheme based on a joint prediction histogram of five separate methods, placed 29 residues in alpha-helices, 71 in beta-pleated sheets, 88 in beta-turns and 55 in aperiodic conformation.

Chemical Phenomena↗
PubMed1980

Mitogenic activity of staphylococcal exfoliative toxin.

Exfoliative toxin from Staphylococcus aureus was mitogenic for murine spleen cells. It was primarily active on T lymphocytes but also significantly stimulated B cells from the spleens of nude mice. The mitogenicity was not affected by simple sugar or alpha-methylpyranosides. N-acetylglucosamine and N-acetylgalactosamine inhibited its effect. Exfoliatin was as powerful a mitogen as the enterotoxins of S. aureus. Some significant differences between the mitogenic activity of the two toxins were demonstrated.

Animals↗
PubMed1979

Purification and characterization of different types of exfoliative toxin from Staphylococcus aureus.

Exfoliative toxin was isolated from strain DI of Staphylococcus aureus using carboxymethyl cellulose and hydroxylapatite chromatography. This purified toxin was compared with that produced by strain TA. The specific biological activity of the two toxins was the same, but they were serologically distinct. These strains have different loci (plasmid or chromosomal) for toxin production; differences were seen in molecular weight and amino acid composition. N-terminal amino acid sequences from the two strains showed significant homology using a single unit alignment shift.

Amino Acid Sequence↗
PubMed1979

Cross-reactions between tryptic polypeptides of staphylococcal enterotoxins B and C.

The strong cross-reactions demonstrated for staphylococcal enterotoxins B (SEB) and C1 (SEC1) by measurement of antigen-binding capacity were reflected in well defined polypeptides obtained by limited tryptic digestion from SEB and SEC1. Two antigenic determinants on each enterotoxin were capable of reacting with heterologous antibody, one on the first 57 amino acids and one on the last 150 residues of the polypeptide backbone. The larger, carboxyl terminal polypeptides bound efficiently to homologous antiserum but about two orders of magnitude less efficiently to heterologous antibody. The amino terminal peptides showed only weak homologous binding but nearly comparable heterologous binding. It is proposed that the determinant on the amino terminal polypeptides is largely responsible for the strong reciprocal binding of the intact enterotoxins and that their low antigen-binding capacity is due to a random or a structurally distorted conformation in solution.

Animals↗