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Biomedical subjects

R Nelson

Publications and source records attributed to R Nelson.

At least 235 records · Page 13Linked to original sources

Analysis of the erythroid phenotype of HEL cells: clonal variation and the effect of inducers.

The erythroid phenotype of HEL cells, before and after the addition of a variety of inducers, was assessed at the cellular and biochemical level. Among 14 inducers used, delta-aminolevulinic acid (delta-ALA) was identified as the most optimal inducer of heme and globin synthesis in HEL cells. The relative synthesis of globin chains produced by HEL cells, mainly gamma and alpha chains with traces of epsilon and zeta chains, was not influenced by the majority of the inducers used. However, delta-ALA and bromodeoxyuridine did increase the relative synthesis of alpha and epsilon chains respectively. Subcloning experiments revealed heterogeneity in the constitutive expression of alpha globin; however, the latter was inducible in all clones by either hemin or delta-ALA. One rare clone of HEL cells was found to produce, in contrast to parental cells, significant amounts of epsilon globin. This clone differed from K562 cells by the absence of any zeta globin expression, thus demonstrating the independent regulation of the two embryonic chains, epsilon and zeta. Changes in the expression of several surface markers specific for erythroid cells were found to accompany the globin accumulation in these cells, and some of these changes appeared to be inducer specific. Thus, the unique globin and nonglobin phenotypic properties of HEL cells and their subclones make them valuable cellular models complementary to the existing K562 cells for studying regulatory aspects of erythroid-specific proteins.

Antigens, Surface↗

In vivo cGMP levels in frog photoreceptor cells as a function of light exposure.

By employing a combination of highly sensitive radioimmunoassays and histochemical techniques, an in vivo time course of cGMP levels has been determined in the outer segment, photoreceptor cell and outer plexiform layers of frog retina. Frogs (Rana pipiens) were dark-adapted overnight and either frozen rapidly (approximately 3 sec) in liquid nitrogen or exposed to periods of light varying between 0.1 sec and 2 hr before freezing. Frozen retinal sections were cut, freeze-dried, and samples of individual layers dissected out and analysed for cGMP. In the outer plexiform layer, there was a 42% drop in cGMP concentration after 2 sec of light (250 ft candles) followed by a 34% rise after 2 min; a steep concentration gradient formed around the layer after the 2 min exposure. In both the outer-segment layer and photoreceptor-cell layer (which includes outer segments, inner segments and outer nuclear layers), cGMP levels declined from a dark value of 56 mumol kg-1 (dry) to 9 mumol kg-1 (dry) as a result of increasing exposure to several types of light source: levels appear to be primarily a function of total ft candle min. Cyclic GMP concentrations at the longest exposures (2 min with a fiber optic light source or 2 hr with fluorescent room light) reached identical minimum levels. In the outer segments, a 15% decrease in cGMP was observed after 0.1 sec of light exposure. Although the freezing time is too long to be able to say whether the 15% decrease in cGMP at the 0.1 sec exposure is involved in transduction, the low identical levels reached gradually after longer exposures appear to indicate that a light-induced biochemical adjustment in cGMP metabolism occurs over a relatively long time period separate from the msec time course of the transduction process.

Animals↗

Further studies of cyclical transmission and antigenic variation of the ILDar 1 serodeme of Trypanosoma vivax.

Antigenic variation in the ILDar 1 serodeme of the naturally rodent-infective stock of West African Trypanosoma vivax has been investigated following cyclical transmission. The immunofluorescent and immune lysis tests were employed with a panel of 39 variant-specific mouse antisera. When antigenically homogeneous, or mixed, populations were transmitted by tsetse flies to goats, the first peak parasitaemias arising in the goats were antigenic mixtures (up to 9 major, and several minor variants being recognized in some cases) from which the ingested variant was absent. Although first peak parasitaemias in similarly infected goats showed some variants in common, there was no obvious relationship between the VAT profiles in different goats. When these populations were expanded in irradiated mice, VAT heterogeneity was maintained with a tendency towards the development of predominant variants in some, but not all, instances. Six additional variants, derived following the growth of bloodstream form ILDat 1.9 in 37 degrees C culture, were also represented in goat and mouse populations. Two further variants, isolated after cyclical development of ILDat 1.9-derived trypanosomes in vitro, were not present in the early parasitaemias in goats and mice.

Animals↗

Adenosine inhibition of calmodulin-sensitive adenylate cyclase from bovine cerebral cortex.

Calmodulin (CaM)-sensitive adenylate cyclase has recently been purified extensively from bovine brain. In this study, the sensitivity of the CaM-sensitive adenylate cyclase to adenosine and adenosine analogs was examined. The highly purified enzyme preparation retained sensitivity to inhibition by adenosine and adenosine analogs with ribose ring modifications, but not to those with purine ring modifications. Adenosine inhibition of this enzyme was not dependent on GTP and was noncompetitive with respect to ATP. Enzyme that had been dissociated from functional guanine nucleotide binding protein interactions by gel filtration in the presence of the zwitterionic detergent 3-[3-(cholamidopropyl)-dimethylammonio]-propanesulfonate and Mn2+ retained sensitivity to adenosine inhibition. The Ki for adenosine inhibition of the CaM-sensitive adenylate cyclase was approximately 2.6 X 10(-4) M. 5'-Guanylylimidodiphosphate and CaM did not affect the Ki of 3'-deoxyadenosine for the enzyme, but the presence of Ca2+ in the millimolar range raised the Ki by a factor of 5. These results show that the CaM-sensitive form of adenylate cyclase from bovine brain is subject to adenosine inhibition, and strongly suggest that this inhibition is due to interaction of ligands with a purine-specific ("P") site located on the catalytic subunit of the enzyme.

Adenosine↗

Neonatal intestinal lactase activity.

The sequential changes in intestinal lactase activity of 40 neonates were measured indirectly from the differential uptake and excretion of lactose and the non-metabolisable disaccharide lactulose contained in formula feeds. A daily decline in urinary lactose:lactulose excretion ratios, reflecting a rise in intestinal lactase activity, followed formula feeding. Percentage decline was related directly to gestation: full term infants displayed a fivefold greater decline in lactosuria than infants with a gestation of 28 weeks during the first 10 days of milk feeding. The difference between lactose:lactulose ingestion and excretion ratios suggests that within five days of starting feeds intestinal hydrolysis of lactose exceeds 98% efficiency, even in very preterm infants.

Aging↗

Construction of the nipple with a mushroom-shaped pedicle.

Construction of the nipple-areolar complex has been the subject of much interest and many papers. We believe that the best way to ensure nipple protrusion is by the entrapment of tissue above the skin surface so that it cannot retract. This, in principle, is similar to creating an irreducible hernia. This technique for nipple construction employs a circular split-thickness island of skin which has its central circulation preserved through its attachment at the new nipple site. This central stalk represents about one-quarter of the total surface area of the constructed areola. The total diameter of the areolar disk is usually determined by the size of the opposite nipple-areolar complex. The new areola is developed from a full-thickness skin graft taken from the area below the inguinal crease. Once removed, it is sutured over the elevated nipple segment with its central island. The full-thickness graft is sutured into place before a small cruciate incision is made in the center. It should be just large enough to permit the delivery of the dermal-epidermal flap on its stalk up through the opening. Nothing more need be done to the raw undersurface of the split-thickness skin. Its raw surface has no place to reattach because its bed is now covered with the full-thickness graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast↗

Genetic brain polypeptide variants in inbred mice and in mouse strains with high and low sensitivity to alcohol.

Twelve genetically determined brain polypeptide charge variants were identified by comparing cerebellar vermis of 7 inbred mouse strains and of mice selectively bred from 8 strains closely related to these 7 ancestral strains and one other for acute behavioral sensitivity to the sedative effects of ethanol. The selectively bred ethanol-sensitive (LS, long sleep) and insensitive (SS, short sleep) mice exhibited different allelic variants at 6 of these 12 gene loci expressed in the cerebellum. Variant polypeptide A1 (81 kdalton, pI 5.6) was shown to be associated with the membrane of synaptosomal mitochondria and to exhibit a basic variant in SS mice that is determined by a dominant allele. Other variant polypeptides showed codominant inheritance in F1 crosses. However, the phenotype of no single one of these brain polypeptides consistently correlated with the ethanol behavioral sensitivity of the 7 inbred mouse strains nor of 8 recombinant inbred (B X D, C57BL X DBA) strains. This finding supports the hypothesis that a substantial amount of inbreeding, leading to random fixation of alleles independent of selection for ethanol sensitivity, occurred during the breeding of the SS and LS mice. The present findings of a lack of a strong association between sleep time and a brain polypeptide variant do not preclude the existence of a major gene effect contributing to variation in acute sensitivity to ethanol but are consistent with reports that multiple loci are responsible for the difference in ethanol sensitivity between SS and LS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Partial deletion of distal 17q.

A newborn female was found to have a deletion of the terminal portion of 17q. Prominent manifestations included microcephaly, apparent hypertelorism, epicanthic folds, a broad nasal bridge with anteverted nostrils, posteriorly angulated ears, micrognathia, widely spaced nipples, arachnodactyly with proximal thumbs, and a coxa vara deformity. The unbalanced translocation was inherited from the mother, who had a reciprocal translocation involving the terminal portions of 2p and 17q. To the best of our knowledge, this is the first report of a liveborn infant with deletion of the distal portion of 17q with the exception of reports of patients with ring chromosome 17.

Abnormalities, Multiple↗

Parasacrococcygeal approach for the resection of retrorectal developmental cysts.

Congenital developmental cysts are the most common retrorectal tumors. Five adult patients, two men and three women, with congenital developmental cysts were operated on via a posterolateral approach through a parasacrococcygeal incision. All wounds healed primarily with no infection or other complications. Recurrent perianal infections and repeated anorectal operations suggest the possibility of retrorectal growths; thus diagnosis requires physician awareness. Computerized tomography is the best preoperative diagnostic test to delineate anatomy and to rule out bony involvement. Because of an infection rate of approximately 30 percent, as well as the presence of symptoms and malignancy in 8 percent of the patients, surgical excision is the treatment of choice. The authors use a posterolateral approach that provides excellent exposure and obviates the need for removal of the coccyx or transection of the sphincter muscle. The authors believe this to be the procedure of choice for excision of retrorectal cystic lesions.

Adult↗

Low-dose dopamine preserves renal blood flow in endotoxin shocked dogs treated with ibuprofen.

Drugs that inhibit prostaglandin (PG) biosynthesis improve hemodynamics and survival in experimental endotoxic and septic shock. The therapeutic utility of these agents in the management of septic patients may be limited, however, by their tendency to decrease renal blood flow (RBF) in animals and humans stressed by experimental manipulations or disease states that promote renal vasoconstriction. In the present study, we addressed this question: can low-dose intravenous (iv) dopamine (4 micrograms/kg/min), a known renal vasodilator, improve renal perfusion in endotoxin-shocked dogs treated with the PG synthesis inhibitor, ibuprofen. RBF was measured in pentobarbital anesthetized dogs using an electromagnetic flow meter. After obtaining baseline hemodynamics, Escherichia coli endotoxin (1.5 mg/kg) was given iv. The dogs were randomized 30 min later into three groups: Group I received saline; Group II received ibuprofen (12.5 mg/kg, iv); Group III received ibuprofen plus dopamine. Comparison of Groups I and II revealed that ibuprofen increased mean arterial pressure (MAP) and systemic vascular resistance (SVR) (P less than 0.0001 and P = 0.002, respectively) and decreased RBF (P = 0.019). Adding low-dose dopamine (Group II vs Group III) did not significantly affect MAP or SVR, but did augment RBF (P less than 0.001). We conclude that low-dose dopamine improves renal hemodynamics in ibuprofen-treated endotoxemic dogs.

6-Ketoprostaglandin F1 alpha↗

Embryology of the middle third of the face.

This article compares the midface appearance of two histological sections, one an embryo at the 6 mm stage of development and another at the 28 mm stage. It demonstrates the considerable cellular differentiation and development that takes place, and suggests that this area is liable to anomalies if the rapid, sequential and considerable amount of growth in this area is disturbed by inherited or environmental factors.

Cell Differentiation↗