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J E Russell

Publications and source records attributed to J E Russell.

At least 37 records · Page 2Linked to original sources
PubMed1996

Developmental silencing of the embryonic zeta-globin gene: concerted action of the promoter and the 3'-flanking region combined with stage-specific silencing by the transcribed segment.

Globin gene switching is a well-described model of eucaryotic developmental control. In the case of the human alpha-globin gene cluster, migration of erythropoietic activity from the embryonic yolk sac to the fetal liver is parallaled by the zeta-globin gene silencing and enhanced expression of the alpha-globin genes. To map critical cis determinants of this switch, the human zeta-globin gene, the alpha-globin gene, and chimeric recombinants were introduced into the mouse genome. Consistent with previous studies, expression of the individual alpha- and zeta-globin transgenes was found to be developmentally appropriate. Contrary to current models, however, the alpha- and zeta-globin gene promoters were not sufficient to establish this control. Instead, full silencing of the zeta-globin gene required the combined activities of this promoter, transcribed region, and 3'-flanking sequences. Individually, the silencing activities of the zeta-globin gene promoter and 3'-flanking region were minimal but increased markedly when both regions were present. The zeta-globin transcribed region appeared to contribute to gene silencing by a mechanism specifically activated in definitive erythroblasts in the fetal liver. These data demonstrate that a complex set of controls, requiring at least three determinants and involving at least two independent mechanisms, is necessary for full developmental silencing of the human zeta-globin gene.

Animals↗
PubMed1993

Functional characterization of the alternatively spliced, placental human growth hormone receptor.

The human growth hormone family of peptide hormones is encoded by five genes, pituitary growth hormone (hGH-N), and four placentally expressed genes, growth hormone variant (hGH-V), chorionic somatomammotropin A and B (hCS-A, hCS-B), and prolactin (hPrl). As part of an effort to define the local effects of the placentally expressed members of the GH/Prl family of hormones on the placenta, we have identified an isoform (hGHRd3) of the growth hormone receptor expressed in the placental villi. hGHRd3 mRNA differs from the liver GHR mRNA by the deletion of a 66-base pair segment encoding exon 3. In this study we show that hGHRd3 mRNA encodes a stable and functional receptor. hGHRd3 mRNA is efficiently translated and processed in a rabbit reticulocyte lysate translation system as well as in an in vivo Xenopus laevis oocyte expression system. In Xenopus oocytes hGHRd3 is stably integrated into the cell membrane and binds and internalizes ligand as efficiently as hGHR. hGHRd3 binds all three of the placentally expressed members of the GH/Prl gene family (hGH-V, hCS, and Prl) as well as both the 22 and 20 kDa isoforms of the pituitary hGH-N. The results of the present study strongly support the expression of a functional hGHRd3 isoreceptor in the placenta which may serve in autocrine, paracrine, and/or endocrine activation.

Animals↗
PubMed1993

Double-stranded RNA triggers generalized translational arrest in Xenopus oocytes.

Controls of gene expression which act at the translational level can be rapidly activated and readily reversed. The impact of double-stranded RNA on translational control is of significant interest as a number of studies point to its ability to directly activate generalized translational arrest. This activity is observed in in vitro systems stimulated by native double-stranded RNAs or synthetic homopolymers and is inferred in virally infected cells in tissue culture. Significantly, however, this activity has never been studied in an intact cell system using RNAs of known secondary structure. In this study we arrest total cellular translation in intact Xenopus oocytes by micro-injecting them with alpha-globin-derivative mRNAs containing defined double-stranded segments. The ability of these mRNAs to directly activate translational arrest in oocytes substantiates the potential role for this activity in vivo and establishes a well-characterized whole cell system for its further study.

Animals↗
PubMed1992

Effect of sodium fluoride on bone density in chickens.

In addition to increasing bone volume, fluoride has been demonstrated to increase ash weight and mineral density. To determine whether newly formed or older bone is most affected by fluoride treatment, bone from chickens receiving fluoridated water was fractionated into lower density (recently formed) and higher density (more mature) specific gravity fractions. Fluoride was administered to the chickens for different lengths of time (4 or 13 weeks) or at varying doses for a 4-week period (0, 4.2, 16.8 mmol/liter drinking water). Fluoride treatment caused a shift in the mineral density profile, showing an increased proportion of mineral distribution in the more mature, higher density fractions. To determine whether this density gradient shift was due to increased maturation rate of bone or decreased resorption and mineralization rates, [3H]proline and 45Ca were injected 5 days and 24 hours prior to sacrifice, respectively. The distributions of both 3H or 45Ca, as percentages of total counts incorporated, were shifted by fluoride treatment into more mature, higher density fractions. Expressing the number of counts as a percent of the bone in each fraction (total hydroxyproline or Ca) revealed an increased incorporation of both 3H and 45Ca into the higher specific gravity fractions 2.0-2.2. These results suggest that fluoride treatment increases bone maturation and the rate of secondary mineralization in the cortical bone. Such changes in the quality of more mature, well-mineralized bone, in humans as well as animals, may have a significant influence on brittleness and strength.

Animals↗
PubMed1992

Bone maturation and resorption by peritoneal macrophages in noninsulin-dependent streptozocin-induced diabetes in the rat.

The existence of osteopenia in noninsulin-dependent diabetes mellitus (NIDDM) is controversial. In this regard rats with a diabetic condition that simulates NIDDM have normal bone mineral content. However, normal total mineral content in bones does not preclude abnormalities in more delicate functions in bones of rats with NIDDM (specifically, bone maturation and response of bone matrix to resorptive activity). To evaluate these functions, bone maturation was studied in tibias from 14-week old male and female rats with streptozocin-induced NIDDM and controls. The ability of macrophages to resorb bone was studied in bone particles that were obtained from femors of male rats with NIDDM and controls. The diabetic rats had the overt NIDDM condition for 8 weeks at the time of the study. We found that bone maturation/mineralization remained intact in the diabetic rats and that response of the bone particles that were obtained from their femors to the resorptive activity of macrophages was similar to that of the bone particles that were obtained from controls. These data suggest that in the rat, a diabetic condition that simulates NIDDM does not alter the physiologic functions of the bone matrix.

Analysis of Variance↗
PubMed1991

Ascorbic acid requirement for optimal flexor tendon repair in vitro.

Numerous studies from our laboratory have defined aspects of the repair process in a lacerated flexor tendon model, both in vivo and in vitro. Inherent in the development of a viable tissue or cell culture model system is the definition of the optimal media environment. Since our laboratory investigations of in vitro flexor tendon repair encompass the formation of numerous extracellular matrix proteins, we have defined the optimal level of ascorbic acid with which to study the tendon wound healing process. The ascorbic acid requirement for proline and lysine hydroxylase activity during collagen biosynthesis is well known, and the importance of this vitamin for matrix proteoglycan synthesis more recently has been appreciated. This report describes the effect of several levels of ascorbic acid on 3H-thymidine incorporation, collagen and noncollagen protein synthesis, and glucose utilization and lactate production. Profundus flexor tendon segments were obtained from young adult New Zealand white rabbits and maintained in organ culture for periods of 1, 2, or 3 weeks. Ascorbic acid concentrations ranged from 50 to 300 micrograms/ml and were added fresh at each 48-h media change. Tendon protein synthesis, glucose metabolism, and cell permeability/viability were significantly correlated with the level of ascorbic acid in the culture medium. The results suggest that ascorbic acid levels in excess of the traditional 50 micrograms/ml are necessary to optimally maintain flexor tendons from adult animals in organ culture with 48-h media and ascorbate changes. Additionally, it may be necessary to determine the precise ascorbic acid requirement for individual tissues, since the specific tissue/cell and species requirement for ascorbate may vary.

Animals↗
PubMed1990

Collagen synthesis during primate flexor tendon repair in vitro.

The concept that flexor tendons have the intrinsic capacity to participate actively in the repair process following laceration has been developed in recent years as the result of experimental studies from numerous laboratories. However, the role of the outer/epitenon and inner/endotenon cell populations with regard to protein synthesis is still controversial. The purpose of this study was to investigate the respective participation of these tendon fibroblast populations in the synthesis of the collagen matrix during in vitro repair of the flexor tendon from nonhuman primates, utilizing immunohistochemical techniques and a Type I procollagen antibody. Zone II profundus flexor tendon segments were obtained from young adult Macaca nemestrina monkeys. One centimeter segments were cultured, either with or without a transverse laceration across 90% of the midsection of the tendon segment. Frozen sections of the cultured tendon segments were reacted with the (mouse monoclonal) Type I procollagen antisera. At all times of culture of the nonlacerated tendon segment, only a few of the epitenon cells along the surface of the tendon and distant from the cut end stained positively for active collagen synthesis. In the lacerated segments, and as early as 9 days of culture and repair, the procollagen reaction product was starting to appear in those cells of the outer epitenon cell layer. These studies support the concept that the inner fibroblasts do actively participate in collagen production. However, it now also appears that a significant degree of collagen synthesis during tendon repair resides in the outer/epitenon layer of cells enveloping the tendon segment, and that the repair response of the flexor tendon in vitro is proportional to the degree of injury.

Animals↗
PubMed1990

A new method for measurement of airway occlusion pressure.

Airway occlusion pressure correlates with central respiratory drive. The airway occlusion pressure (P0.1) may be an excellent predictor of the ability of patients with obstructive lung disease to wean from mechanical ventilation. We describe a new method for measuring P0.1 using digitized signals generated from standard respiratory equipment and a computer program to automatically determine P0.1 values. The accuracy of this new method was tested by comparison with standard analog recorder methods using a mechanical lung model, in ventilated patients in an intensive care unit, and in normal volunteers. In all settings, excellent correlation was obtained between P0.1 measurements by the digital Servo and standard analog methods (r = 0.99). This new method permits accurate and automatic determination of P0.1 in ventilated patients using standard respiratory equipment. The rapid response and ease of use of this method should enable evaluation of a number of physiologic variables involved in respiratory control in ventilated and nonventilated patients.

Airway Resistance↗
PubMed1990

Analysis of individual variability among older adults on the Stroop Color Word Interference Test.

The present study examines systematic variation in the pattern of response to the Stroop test among a sample of older adults (N = 41), as well as the extent to which various configural patterns of response are related to other individual difference factors. Pattern analysis identified four reasonably prototypic patterns of performance. Three significant discriminant functions, capable of differentiating the four response patterns, were significantly and uniquely related to age, level of cautiousness, and verbal intelligence, respectively. The analyses suggest that performance on the Stroop test is multidimensional with significant variation among older adults, and that different components of performance are differentially related to unique individual difference variables. The findings reinforce the importance of recognizing and understanding the nature of individual variation among elderly individuals in aging research.

Age Factors↗
PubMed1989

Myeloperoxidase-positive acute megakaryoblastic leukemia.

Acute megakaryoblastic leukemia (FABM7) is an unusual but well recognized form of acute myelogenous leukemia in which the bone marrow blast cells are phenotypically recognized by the demonstration of cytoplasmic platelet peroxidase or surface staining for the IIb/IIIa platelet-specific glycoprotein. Herein, the authors report a case of acute megakaryoblastic leukemia that satisfies the accepted French-American-British criteria and in which the blast cells also exhibit evidence of myeloid differentiation, including surface MY7 (CD13) by flow cytometry and immunocytochemical positivity for myeloperoxidase. These findings suggest that megakaryoblasts may be closely related to myelomonoblasts, that they have the potential to partially differentiate along multiple phenotypic lines, and that aberrant phenotypes can occur that do not correspond to known stages of normal maturation. The authors illustrate the difficulty in classification of these aberrant phenotypes by standard cytochemical and morphologic criteria.

Cell Membrane↗
PubMed1989

Biochemical evaluation of organ cultures from primate flexor tendons.

Recently our laboratory has reported, in a lacerated flexor tendon model, that the "early turnover" phase of the repair process extends for a longer period of time in vivo than previously documented. The extensive turnover of the collagenous matrix was consistent with the presence of collagenolytic activity in repairing tendon tissue and suggested a possible regulatory role for neutral metalloproteinases in flexor tendon repair. However, these in vivo observations could not distinguish the relative contribution by the tendon fibroblasts from that of the surrounding sheath and vascular tissue elements. To further define these interrelationships, the present study investigates the repair process of the flexor tendon in an in vitro tissue culture environment. The sequential changes in matrix formation were defined (i.e., proteoglycans/glycosaminoglycans, glycoproteins, and collagenous proteins). The concomitant production of neutral metalloproteinases as well as prostaglandin E2 was determined in relation to net tissue repair. Profundus flexor tendon segments were obtained from young adult Macaca nemestrina monkeys and maintained in organ culture for periods from 4 days through 9 weeks. Initially (at 2 wks) there was an increase in both sulfated and nonsulfated glycosaminoglycans, which preceded the onset of maximal collagen protein formation. By 6 and 9 weeks of in vitro repair, of the lacerated tendon segments, there was a significant increase in net collagen formation. Neutral metalloproteinase activity increased early in the repair period, from the 4th to 9th day, and decreased thereafter through the 9th week of culture. Functionally the enzyme appeared to be a gelatinase. The temporal pattern of in vitro collagen synthesis in relation to the gelatinase activity support the hypothesis that regulation of this enzyme(s) may be a critical factor in mediating the flexor tendon response to injury.

Animals↗
PubMed1988

Bone cell populations and histomorphometric correlates to function.

A circadian context has been used to develop information about the proliferative and functional behavior of the cell populations that function to model the long bones of growing rats. We asked: Are the proliferating cells in the growth cartilages and diaphyseal bone of young adult growing rats distributed within single or multiple populations? Can cytomorphometry (TEM-C) be used to determine ultrastructural correlates to the well-defined circadian rhythm of matrix formation displayed by functionally synchronous populations of metaphyseal osteoblasts? Can TEM-C reveal changes in osteoclast ultrastructure that could index a biological rhythm for osteoclastic bone mineralysis/resorption? Kinetic results derived from multiple radiothymidine labeling (DNA synthesis) support the single population model for chondrocytes and diaphyseal osteoprogenitor cells. TEM-C studies at the midpoints of the daily light and dark spans show that osteoblast RER-membrane development and cysternal volumes are maximal at the recorded daytime peak of net collagen synthesis. The extent of metaphyseal osteoclast surface ruffling (mineralysis) is also twofold greater during the day than the night--an observation supporting the concept that bone formation and resorption activities are coupled.

Animals↗
PubMed1988

Regional differences in matrix formation in the healing flexor tendon.

In 20 white leghorn chickens, the effect of proximity (proximal vs. distal) to the repair site and the effect of sheath excision versus sheath repair on biochemical matrix formation in the healing zone 2 flexor tendon were studied. In 14 animals, the profundus tendon of the long toe on both feet was lacerated and repaired in zone 2. In the right foot, the sheath was repaired, and on the left foot, the sheath was excised. Segments proximal and distal to the laceration site were studied at six weeks postrepair compared to control segments. Sheath excision versus sheath repair had no effect on the net matrix formation of the healing flexor tendon. A higher DNA content and lower hydroxyproline and hexosamine contents were present in the healing tendons, indicating the healing process was not complete at six weeks. Sheath excision versus sheath repair had no effect on net matrix formation in the healing tendon. There is no difference in DNA content or glycosaminoglycan content in the proximal versus distal segments. There was a significantly greater net hydroxyproline content in the proximal segment versus the distal segment of the healing tendon, which was not present in similar control segments. These results support the concept that the zone 2 flexor tendon does not respond to injury as a homogeneous structure.

Animals↗
PubMed1988

The effect of vascularization on avian flexor tendon repair. A biochemical study.

Although it has been demonstrated in experimental animals that vascular perfusion functions less effectively than diffusion as a nutrient pathway to the uninjured flexor tendon, it is recognized that the nutritional requirements of an injured flexor tendon may be different. The present study examines several biochemical parameters of avian flexor tendon repair, during a six-week period, in the presence of an intact vinculum longum and with the vinculum longum ligated. Formation of collagen/noncollagen protein, glycosaminoglycan synthesis, and tissue levels of both DNA and hexosamine were quantified. The absence of the vincular blood supply did not affect the levels of total DNA and hexosamine, did not alter the pattern of either protein or glycosaminoglycan formation in the early healing phase, and did not impair the overall synthesis of collagen and noncollagen protein throughout the six-week study period. However, the pattern of collagen and noncollagen protein synthesis differed in lacerated tendons during the period of repair; noncollagen protein synthesis peaked at ten days, while collagen synthesis increased uniformly throughout the 42-day period of study. There was a notable decrease in total matrix hydroxyproline (collagen) during repair, which continued throughout the entire first three weeks after laceration. Thus, the actual percentage of collagen synthesis decreased during the first three weeks of repair and began to return to its normal uninjured level by the sixth week.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cautiousness and visual selective attention performance among older adults.

Cautiousness has been implicated in the literature as a possible factor responsible for observed performance decrements among older adults in a number of research paradigms. This study sought to assess whether the speed and accuracy of performance on a perceptual-cognitive task (the Stroop Color-Word Interference Test) differed significantly for more and less cautious older adults. The participants (N = 41), ranging from 55 to 81 years of age, were classified as either more cautious (n = 20) or less cautious (n = 21) on the basis of their responses on a personality test. Results indicated that cautiousness among older adults was manifested more in terms of the accuracy of response (fewer errors of commission) than in terms of the speed of response, and that level of cautiousness increased with increasing age.

Aged↗
PubMed1987

Hydrogen peroxide inhibits glucose metabolism and collagen synthesis in bone.

Effects of H2O2 on bone were evaluated in an organ culture system. Tibiae from chick embryos were incubated for up to 3 days in culture medium containing 0.07 to 20 mM H2O2. Glucose metabolism was monitored by measuring lactate production and oxygen consumption, and collagen synthesis was determined by hydroxylation of proline. In addition to markedly inhibiting these parameters, H2O2 also decreased bone weight and alkaline phosphatase activity. Multiple exposures to H2O2 were somewhat more effective than a single exposure. Since H2O2 inhibits bone at low concentrations in vitro, the results suggest that the potential for harmful effects of H2O2 in the oral cavity should be investigated.

Animals↗
PubMed1986

Effects of age and estrogen on calcium absorption in the rat.

In order to differentiate the relative effects of age and estrogen on rates of calcium absorption and serum levels of parathyroid hormone and calcitonin, the effect of oophorectomy with and without estrogen replacement (2 weeks) was studied in rats for 30- or 120-day periods. Whereas oophorectomy for 30 days resulted in a significant decrease in serum calcium and an increase in serum phosphate, no change in either calcium or phosphate was observed in the 120-day oophorectomized animals. iPTH decreased in both the 30- and 120-day oophorectomized animals although these changes were not significant at the .05 level. Whereas no significant change in basal circulating calcitonin occurred in the 30-day oophorectomized rats, it decreased significantly in the older animals following the ablative procedure. Forty-five days following estrogen deprivation, calcitonin release to a calcium secretagogue was significantly blunted. Intestinal calcium absorption decreased with age, and unlike the increments in calcium absorption observed in the younger estrogen-repleted, 30-day oophorectomized rat, no change in calcium absorption was observed when estrogens were administered to the older, 120-day oophorectomized rat. The accumulated data suggest that the effects of estrogen loss on the hormonal control of bone metabolism and calcium absorption are age dependent, and that estrogen contributes significantly to changes in calcium homeostasis observed in the maturing rat.

Aging↗