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B J Brown

Publications and source records attributed to B J Brown.

At least 73 records · Page 4Linked to original sources
PubMed1988

A survey of neurological mutant mice. I. Lipid composition of myelinated tissue in known myelin mutants.

The lipids of white matter and peripheral nerve from mutant mice with known myelin deficiencies were analyzed by one- and two-dimensional high-performance thin-layer chromatography and quantitated by densitometry. In optic nerve, the mutants jp/Y, jpmsd/Y, qk/qk, shi/shi and shimld/shimld, which have severe central nervous system (CNS) myelin deficiency, had a common pattern of lipid loss: cerebrosides and sulfatides (hydroxy and nonhydroxy forms) were generally reduced by 70-95% or more; most phospholipids were diminished by 15-55%, and cholesterol was reduced by 35-60%. Only in the CNS of jp/Y and jpmsd/Y did cholesterol ester accumulate. In peripheral nerve, the lipid composition varied markedly among these mutants. In jp/Y there was no change, while in jpmsd/Y there was a 5-15% loss among the phospholipids and cholesterol. Homozygous qk had reductions of 75-85% in the nonhydroxy forms of cerebroside and sulfatide, a 130% increase in hydroxy sulfatide, and a 55% loss of sphingomyelin. In shi/shi and shimld/shimld homozygotes, the glycolipids were altered by +/- 20%, most phospholipids and cholesterol were reduced by 5-15%, and sphingomyelin was reduced by 40%. Tr and TrJ showed 35-90% reductions in most lipid classes of the peripheral nervous system; CNS lipid composition was normal. Homozygous twi had a uniform loss of most lipid classes in both optic (generally 10-20%) and trigeminal nerves (generally 40-55%); cerebrosides did not accumulate in these tissues. dy/dy had a 10-20% reduction of cerebrosides in trigeminal nerve trunk. The CNS of dy homozygotes had 10-35% increases in specific classes of glycolipids and phospholipids, and in cholesterol. None of the mutants showed detectable levels of lysophospholipids or other unusual lipid species. The fractions of ethanolamine and choline phosphatides in the plasmalogen form were close to normal in all mutants.

Animals↗
PubMed1988

A survey of neurological mutant mice. II. Lipid composition of myelinated tissue in possible myelin mutants.

The lipids of white matter and peripheral nerve from neurological mutant mice with possible myelin abnormalities were analyzed by thin-layer chromatography and quantitated by densitometry. Eight mutants had major abnormalities in the central nervous system (CNS) and/or peripheral nervous system (PNS) tissues examined (optic nerve, and trigeminal and sciatic nerves). In the optic nerve of axJ/axJ, there were increases of 20-30% in the levels of the major phospholipids; peripheral nerve was normal. In bc3J/bc3J CNS, the major phospholipids and cholesterol were increased by 25-40%; the PNS was normal. In myd/myd CNS, there were increases of about 20% in the levels of both forms of cerebrosides and in the major phospholipids; in the PNS the lipids were normal. ot/ot CNS had 20-40% reductions of all the glycolipids and minor alterations in some of the phospholipids and cholesterol; the PNS had 20% losses of both forms of cerebrosides. In the PNS of ji/ji, there were decreases of 10-40% among the glycolipids and of 15-25% in three of the major phospholipids; the CNS was virtually normal. In the PNS of dtJ/dtJ, vb/vb and wr/wr, almost all lipids were significantly decreased. The CNS of dtJ/dtJ and vb/vb were normal; wr/wr had minor reductions of certain glycolipids and phospholipids. Six mutants had relatively minor lipid abnormalities in their myelinated tissues. In cr/cr PNS, there were elevated levels of the cerebrosides and major phospholipids; the CNS was virtually normal. In db/db CNS and PNS, there were reduced levels of the nonhydroxy forms of cerebroside and sulfatide. The major change in htr/htr was the elevation of all the glycolipids in the CNS. In the CNS of Lc/+, nonhydroxy cerebroside was reduced. In shm/shm PNS, nonhydroxy sulfatide was elevated and there were small decreases in some of the phospholipids. wl/wl CNS showed decreases among most of the glycolipids. Mutants homozygous for du, mto, spa and tg had virtually normal lipid levels in both the optic and peripheral nerves. Cholesterol ester, lysophospholipids and other unusual lipid species were not detected in any of the mutants. The plasmalogen forms of ethanolamine and choline phosphatides were at normal levels in all mutants that otherwise had significant alterations among their lipids. Although many alterations in lipid composition were found in these mutants, the changes were moderate compared to the classical myelin mutants and indicate that none of the mutants are severely myelin-deficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The dean as mentor.

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Administrative Personnel↗
PubMed1983

Evaluation of some anthracycline antibiotics in an in vivo model for studying drug-induced human leukemia cell differentiation.

Human acute promyelocytic leukemia cells (HL-60) were induced to undergo terminal differentiation by treatment in vivo with marcellomycin. This was accomplished by cloning HL-60 cells in 0.3% agar in diffusion chambers, which were subsequently implanted in the peritoneal cavities of mice. These animals were given injections i.v. with anthracycline antibiotics, and the chambers were transferred to a second recipient 24 hr later. After an additional 8 days, the chambers were removed, the cloning efficiency was determined, and colonies were scored for the presence of differentiated cells based on their ability to reduce nitro blue tetrazolium (NBT). Marcellomycin produced dose-dependent decreases in cloning efficiency and increases in the number of differentiated cells present in chambers. At all dose levels of marcellomycin tested, three types of colonies were observed; these were colonies consisting entirely of undifferentiated cells and approximately equal numbers of colonies consisting of solely differentiated cells and those with mixtures of both differentiated and undifferentiated cells. An 8-fold increase in colonies containing differentiated cells (both pure and mixed) was observed after a single injection of marcellomycin (10 mg/kg), a dose which reduced cloning efficiency by 40%. At that dosage level, aclacinomycin A also induced differentiation, while doxorubicin was ineffective, a finding consistent with the effects of these anthracyclines on HL-60 cells in suspension culture. In addition to the functional changes accompanying differentiation, commitment was characterized by a limitation in proliferative potential. Thus, the average size of uniform NBT-positive colonies was approximately 16 cells, and few clones of NBT-positive cells greater than 32 cells in number were observed; this contrasted with NBT-negative clones which contained up to 100 cells. This finding suggests that HL-60 cells undergo an average of four and a maximum of five divisions upon commitment to granulocytic differentiation. The in vivo system described may be useful in further evaluation of differentiation-inducing agents for therapeutic potential after an initial in vitro screen to identify active compounds.

Aclarubicin↗
PubMed1983

Sensitivity of bone marrow hematopoietic colony-forming cells from mice, dogs, and humans to carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin and its relationship to clinical toxicity.

The sensitivity of bone marrow granulocyte-macrophage colony-forming cells to 4 anthracyclines, carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin, was studied using the agar diffusion chamber technique which allows exposure of target cells to drug metabolized by the chamber-bearing host after i.v. injection. Colony-forming cells from mice, dogs, and humans were all found to have exponential dose-response curves for the agents studied, with variation of the slopes between species and agents. Species sensitivities as determined by the assay related well to the available toxicological and clinical data for specific drugs. The rank order of sensitivity of human marrow colony-forming cells to five anthracyclines tested in this and a previous study related very closely to doses producing moderate leukopenia in Phase I and II clinical studies. A dose of 200 mg/sq m of N,N-dibenzyldaunorubicin would be expected to produce moderate leukopenia in future clinical trials. This assay may be useful in predicting human bone marrow toxicity of new agents before actual clinical trial because of the ability to study the survival of human colony-forming cells directly.

Aclarubicin↗
PubMed1982

A simplified system of human milk banking.

A simplified system of human milk banking, from milk supplied from home or hospital, has been evaluated for use in a neonatal intensive care unit. Twenty milk samples were obtained at a single expression using a standard hand pump and divided into three parts. Analyses were performed on the raw milk and on samples stored at -20 degrees C for 1 week and 1 month. No pathogens were isolated from any samples and the counts of Staphylococcus albus in the raw milk remained unchanged after storage. 19% of the cells in the original milk survived freezing and remained viable. There was a loss of bacteriostatic activity after storage for one month but significantly less than that caused by pasteurization. No change in levels of IgA, IgM, IgF, lactoferrin, lysozyme, C3 and C4 was apparent and concentrations of amino acids and fatty acids also remained unchanged after storage. We conclude that milk can be safely and conveniently stored by this method without loss or damage to the components of raw breast milk important for preterm and sick infants.

Amino Acids↗
PubMed1982

Transfer of Bacillus thuringiensis plasmids coding for delta-endotoxin among strains of B. thuringiensis and B. cereus.

The recently discovered high-frequency transfer of plasmids between strains of Bacillus thuringiensis was used to study the genetic relationship between plasmids and production of the insecticidal delta-endotoxin crystal. Three strains of B. thuringiensis transmitted the Cry+ (crystal-producing) phenotype to Cry- (acrystalliferous) B. thuringiensis recipients. Agarose gel electrophoresis showed that one specific plasmid from each donor strain was always present in Cry+ "transcipients." The size of the transmissible crystal-coding plasmid varied with the donor strain, being 75 MDal (megadaltons) in size in HD-2, 50 MDal in HD-73, and 44 MDal in HD-263. Immunological analysis showed the Cry+ transcipients to be hybrid strains, having flagella of the recipient serotype and crystals of the donor serotype. These results demonstrate that the structural genes for the delta-endotoxin are plasmid borne. Crystal-coding plasmids also transferred into two strains of the related species Bacillus cereus and yielded transcipients that produced crystals of the same antigenicity as the donor strain.

Bacillus cereus↗
PubMed1982

Creativity.

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Creativity↗