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Biomedical subjects

C Crowley

Publications and source records attributed to C Crowley.

At least 37 records · Page 2Linked to original sources
PubMed1986

Maternal phenylketonuria.

Pregnant women with untreated phenylketonuria (PKU) with blood phenylalanine levels greater than 1200 mumol/L usually give birth to offspring with congenital birth defects, including microcephaly, cardiac defects and mental retardation. According to Mabry and Levy, hyperphenylalaninaemic (HPA) women with blood phenylalanine levels between 600 and 1200 mumol/L also have an increased risk to their offspring. To study this problem further, the National Institute of Child Health and Human Development has established a collaborative study for 7 years to elucidate a proper treatment programme for these women.

Adult↗
PubMed1983

Abnormal gamma-glutamylcysteine synthetase activities in sheep red blood cells.

Red blood cell gamma-glutamylcysteine synthetase (GC-S) activities and glutathione (GSH) concentrations were investigated in pure-bred Finnish Landrace, Tasmanian Merino, and Finnish Landrace X Tasmanian Merino sheep. Previous studies were confirmed that a dominant gene (L) at the GSH locus leads to partial GC-S and GSH deficiency, while a recessive gene (h) at the Tr locus codes for defective red cell amino acid transport, concomitant GSH deficiency, and significantly elevated levels of GC-S. In addition, new results are presented which suggest that there is a dominant gene (A) at another locus distinct from GSH and Tr (provisionally designated GC-S) which has a marked epistatic enhancing effect on measured GC-S activities.

Animals↗
PubMed1981

Red cell glutathione deficiency: clinical and biochemical investigations using sheep as an experimental model system.

The biochemical properties of red cells from normal sheep and sheep with three types of red cell glutathione (GSH)-deficiency were compared. One deficiency was due to an impaired transport system for amino acids (lesion 1), one was the result of a diminished activity of gamma-glutamyl cysteine synthetase (GC-S) (lesion 2) and the third was a combined deficiency produced by selective breeding to give animals with both lesions 1 and 2. Under normal husbandry conditions no clinical symptoms were apparent in sheep with lesion 2, but red cells from sheep with lesion 1 and lesions 1 + 2 showed an increased osmotic fragility, a greater tendency to form Heinz bodies and a shorter potential life span than normal. These deficiencies were not found in tissues other than blood. Normal and GSH-deficient red cells had the expected low concentrations of 5-oxoproline. The effects of the toxic agents phenylhydrazine, s-methylcysteine sulphoxide and nitrite in vivo were measured in sheep of the different types. GSH-deficient sheep responded earlier and more dramatically than normal sheep, showing greater methaemoglobin formation, and for phenylhydrazine and s-methylcysteine sulphoxide, more severe anaemia. Sheep with the combined lesions were in general the most susceptible, but even they had the ability to recover from moderately severe oxidative challenge.

Anemia↗
PubMed1980

The effects of laminin on the growth and differentiation of embryonal carcinoma cells in defined media.

In this paper we have examined the growth and differentiation of the embryonal carcinoma cell line, F9, in the defined medium EM-3 at low density. We show that the growth of F9 and their differentiated cells (F9-diff) in EM-3 is strongly density dependent. At low cell densities the growth of both cell types is severely limited and most of the cells do not survive. Although this poses a problem for working with F9 and F9-diff in EM-3, it provides a convenient assay for identifying molecules that support their growth at low density. Using this assay, we have determined that laminin, a newly isolated glycoprotein of basement membranes, significantly improves the growth and short-term survival of both F9 and F9-diff. However, addition of laminin to EM-3 is insufficient to promote the clonal growth of these cell types. Our findings also indicate that laminin promotes the attachment of F9 and F9-diff in defined media. On the basis of our results, we propose an attachment function for laminin during the early stages of mammalian development.

Animals↗
PubMed1980

Growth and differentiation of embryonal carcinoma cell line F9 in defined media.

This paper reports the growth and differentiation of the mouse embryonal carcinoma cell line F9 in completely defined culture media. The defined growth medium, referred to as EM-3, contains plasma fibronectin, insulin, and transferrin in place of serum. F9 cells cultured in EM-3 for over 15 generations retain their ability to form tumors and to differentiate. Fibronectin is essential for the attachment of F9 cells in defined media and its effect can be blocked with affinity-purified anti-fibronectin. When retinoic acid was added to EM-3, the F9 cells differentiated. The majority of the the newly formed cells differed from patient F9 cell two major respects: (i) they were morphologically different; and (ii) they secreted plasminogen activator, and the secretion was stimulated by dibutyrlyl adenosine cyclic monophosphate.

Animals↗
PubMed1979

Retinoic acid stimulation of the induction of mouse killer T-cells in allogeneic and syngeneic systems.

The ability of retinoic acid (RA), a potent antitumor agent, to stimulate cell-mediated cytotoxicity (CMC) in mice was investigated. Low doses of RA (5-300 micrograms/mouse/day) administered ip into C57BL/6 mice for 5 days daily or for 1--3 months three times a week before immunization in vivo or in vitro with allogeneic BALB/c S194 myeloma cells led to an enhanced cytotoxic activity of their spleen effector cells. Similarly, in a syngeneic situation injection of RA into C57BL/6 or BALB/c mice before in vitro challenge with EL 4 (C57BL/6) or S194 (BALB/c) tumor cells strongly stimulated CMC. The enhanced cytotoxic activity was effected by thymus-derived lymphocytes (T-cells) and specific for the H-2 histocompatibility antigens in the case of the allogeneic sensitization or specific for tumor antigens in the case of the syngeneic sensitization. Because RA had no effect on the effector step of CMC, RA likely enhanced the induction step of T-CMC. The action of RA was antigen-dependent, and it is therefore a true adjuvant rather than a nonspecific stimulator or polyclonal activator of cytotoxic T-cells.

Animals↗
PubMed1978

NADH diaphorase as a genetic marker for sheep red cells.

Three NADH diaphorase phenotypes were observed in the red cells of sheep. Breeding data indicated that this polymorphism was under the control of two autosomal codominant alleles, designated DiaF and DiaS. Phenotype Dia F had significantly lower NADH diaphorase activity than phenotype Dia S. The frequency of DiaF and DiaS was determined in 9 different breeds.

Alleles↗
PubMed1975

Spectrofluorometric determination of the antibiotic lasalocid in blood.

A spectrofluorometric assay was developed for the determination of the antibiotic lasalocid in dog blood, based on the intrinsic fluorescence of the compound in ethyl acetate. The assay can measure "total" levels of drug and any metabolites present. The specificity of the assay was verified by TLC separation of the dog blood extract, which indicated the presence of only intact drug. The overall recovery (+/- SD) of lasalocid was 62.0 +/- 3.6% in the concentration range of 1.0-10 mug of compound/ml of dog blood. The sensitivity of the assay is 0.5 mug/ml. The assay was applied to the determination of blood levels of lasalocid in the dog following the intravenous administration of a 5-mg/kg dose.

Animals↗
PubMedDate not supplied

Mitochondrial perturbation attenuates bile acid-induced cytotoxicity.

Hydrophobic bile acids such as deoxycholate (DOC) are known to damage liver cells during cholestasis and promote colon cancer. Cellular stresses induced by bile acids, which include mitochondrial and endoplasmic reticulum (ER) stresses, can result in apoptosis. We found that inhibition of mitochondrial complexes I-V with rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, myxothiazol or oligomycin strongly protected against DOC-induced apoptosis of HCT-116 cells. To understand the mechanism of this protection, we explored the ability of these specific inhibitors to reduce DOC-induced mitochondrial and ER stresses. Different inhibitors markedly reduced DOC-induction of mitochondrial condensation, the DOC-induced decrease in mitochondrial membrane potential and the DOC-induced dilatation of the ER (evidence of ER stress). A dramatic induction of nucleolar segregation by antimycin A and myxothiazol, two distinct complex III inhibitors, was also observed. These findings strongly implicate mitochondrial crosstalk with apoptotic signaling pathways and mitochondrial-nucleolar crosstalk in the development of apoptosis resistance in the colon.

Antimycin A↗