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Biomedical subjects

C E Nelson

Publications and source records attributed to C E Nelson.

At least 19 recordsLinked to original sources

Control of a genetic regulatory network by a selector gene.

The formation of many complex structures is controlled by a special class of transcription factors encoded by selector genes. It is shown that SCALLOPED, the DNA binding component of the selector protein complex for the Drosophila wing field, binds to and directly regulates the cis-regulatory elements of many individual target genes within the genetic regulatory network controlling wing development. Furthermore, combinations of binding sites for SCALLOPED and transcriptional effectors of signaling pathways are necessary and sufficient to specify wing-specific responses to different signaling pathways. The obligate integration of selector and signaling protein inputs on cis-regulatory DNA may be a general mechanism by which selector proteins control extensive genetic regulatory networks during development.

Animals↗

Concentrations of steroid hormones in layers and biopsies of chelonian egg yolks.

The actions of circulating hormones, although relatively well understood for adults, are largely unknown for their developing embryos. Transfer of maternal hormones to the egg is known to occur in oviparous species, and recently the presence of hormonally heterogeneous yolk layers has been described in two avian species. To investigate the possibility of a similar phenomenon occurring in chelonian species, egg yolk layers were analyzed in the painted turtle (Chrysemys picta marginata) and the red-eared slider turtle (Trachemys scripta elegans), two species that exhibit temperature-dependent sex determination. There was a similar pattern of hormonally heterogeneous yolk layers in both species: concentrations of progesterone and testosterone were significantly higher in the external yolk layer while concentrations of 17beta-estradiol were significantly higher in the intermediate and internal layers. This pattern of hormone deposition concurs with previously published studies of plasma hormone profiles from females of temperate-zone turtle species. Yolks of freshly laid eggs were also sampled using a biopsy technique to examine the concordance of early yolk hormone concentrations and offspring sex. No relationship was found between yolk hormone concentrations and individual offspring sex. Previous work showing that maternally derived yolk estradiol concentrations are correlated with female-biased sex ratios was, however, replicated. These findings suggest that offspring sex is influenced, in part, by the maternal hormone environment.

Animals↗

Environmental sex determination in a reptile varies seasonally and with yolk hormones.

Most hypotheses that have been put forward in order to explain the persistence of environmental sex determination (ESD) in reptiles assume a relatively fixed association of sex with temperature-induced phenotype and no maternal influence on offspring sex. Here we demonstrate the association of maternally derived yolk hormone levels with the offspring sex ratio and describe two new aspects of temperature-dependent sex determination (TSD), i.e. seasonal variation in both thermal response and yolk steroid levels. Eggs from painted turtles (Chrysemys picta) were incubated at 28 degrees C. The hatchling sex ratio at 28 degrees C (i.e. the phenotypic reaction norm for sex at 28 degrees C) shifted seasonally from ca. 72% male to ca. 76% female. Yolk oestradiol (E2) increased seasonally while testosterone (T) decreased. The proportion of males in a clutch decreased as E2 levels increased and the E2:T ratio increased. These new findings are discussed in relation to heritability and adaptive explanations for the persistence of ESD in reptiles. Maternally derived yolk hormones may provide a mechanism for the seasonal shift in the sex ratio which in turn may help explain the persistence of ESD in reptiles. They may also explain those clutches of other reptiles with TSD that fail to yield only males at maximally masculinizing conditions.

Animals↗

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.

Administration, Intravesical↗

The challenge hypothesis and seasonal changes in aggression and steroids in male northern fence lizards (Sceloporus undulatus hyacinthinus).

The challenge hypothesis has been very successful in explaining patterns of testosterone secretion in response to social stimuli in avian species. However, there have been few studies in nonavian vertebrates. We tested the challenge hypothesis in male northern fence lizards (Sceloporus undulatus hyacinthinus). These males are highly territorial and nonparental. Consequently, the challenge hypothesis predicts that plasma testosterone concentrations will be insensitive to aggressive interactions. Testosterone concentrations indeed were not significantly affected by either a short (3-15 min) simulated territorial intrusion ("challenge") in June or a longer (50-60 min) intrusion in July. Levels of corticosterone were elevated in challenged males in the long, but not the short, intrusion. Challenged males displayed significantly more intense territorial behaviors than did unchallenged control males. The intensity of territorial behavior changed significantly across the active season and was positively related to testosterone concentrations. Thus, while testosterone concentrations do not appear to be involved in rapid changes in aggressive behavior in the fence lizard, they probably are important in larger-scale behavioral changes throughout the season.

Aggression↗

Analysis of Hox gene expression in the chick limb bud.

The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.

Amino Acid Sequence↗

Sonic hedgehog regulates patterning in early embryos.

Recently, a new family of genes, homologues of the Drosophila segment polarity gene hedgehog, has been cloned in vertebrates. One of them, Sonic hedgehog, is expressed in tissues that are known to be inductive centres for patterning early embryos, implicating Sonic hedgehog as an important signal in development. Functional experiments have demonstrated that Sonic hedgehog acts as a signalling molecule in patterning the anterior-posterior axis of the limb. By misexpression of Sonic hedgehog we show that Sonic hedgehog induces expression of Hoxd genes, known to be involved in patterning of the anterior-posterior axis of the limb, and Bmp-2, which might act as a secondary signal. We also demonstrate that Sonic hedgehog is not sufficient for these inductions. In fact, a signal from the mesoderm, Sonic hedgehog, and a signal from the ectoderm, Fgf-4, are required for the induction of Hoxd genes and Bmp-2.

Animals↗

Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut.

Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

Animals↗

Hox genes and the evolution of vertebrate axial morphology.

A common form of evolutionary variation between vertebrate taxa is the different numbers of segments that contribute to various regions of the anterior-posterior axis; cervical vertebrae, thoracic vertebrae, etc. The term 'transposition' is used to describe this phenomenon. Genetic experiments with homeotic genes in mice have demonstrated that Hox genes are in part responsible for the specification of segmental identity along the anterior-posterior axis, and it has been proposed that an axial Hox code determines the morphology of individual vertebrae (Kessel, M. and Gruss, P. (1990) Science 249, 347-379). This paper presents a comparative study of the developmental patterns of homeobox gene expression and developmental morphology between animals that have homologous regulatory genes but different morphologies. The axial expression boundaries of 23 Hox genes were examined in the paraxial mesoderm of chick, and 16 in mouse embryos by in situ hybridization and immunolocalization techniques. Hox gene anterior expression boundaries were found to be transposed in concert with morphological boundaries. This data contributes a mechanistic level to the assumed homology of these regions in vertebrates. The recognition of mechanistic homology supports the historical homology of basic patterning mechanisms between all organisms that share these genes.

Animals↗

Involvement of adult rehabilitation patients in setting occupational therapy goals.

OBJECTIVE: This preliminary study was designed to determine whether occupational therapists involve patients and their families in a goal-setting process and, if so, to identify the methods used. METHOD: Thirty registered occupational therapists practicing in adult physical rehabilitation settings were audiotaped during an initial evaluation. Researchers reviewed corresponding documentation and interviewed each subject. Twenty-three patient and family involvement criteria were generated from standards developed by accreditation commissions and health care professions. RESULTS: Data revealed that although subjects did involve patients and families in a goal-setting process, a number of criteria were not attempted, thus much potential for involvement was unrealized. Subjects with scores above and below one standard deviation from the mean were identified to determine which patient participation criteria had the highest discrepancies. Discrepancies included (a) verbal preparation of the patient and family for initial and ongoing treatment, purposes and procedures of evaluation and treatment, and potential outcomes of treatment, (b) attempts to elicit the patient's concerns, and (c) collaboration with the patient to establish treatment goals. CONCLUSION: Factors that might have influenced subjects' use of a patient participation approach included the application of a specific theory or technique, time constraints, patient's age, and assumptions about the patient's cognitive status.

Adult↗

Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud.

Proper limb growth and patterning requires signals from the zone of polarizing activity in the posterior mesoderm and from the overlying apical ectodermal ridge (AER). Sonic hedgehog and Fgf-4, respectively, have recently been identified as candidates for these signals. We have dissected the roles of these secreted proteins in early limb development by ectopically regulating their activities in a number of surgical contexts. Our results indicate that Sonic hedgehog initiates expression of secondary signaling molecules, including Bmp-2 in the mesoderm and Fgf-4 in the ectoderm. The mesoderm requires ectodermally derived competence factors, which include Fgf-4, to activate target gene expression in response to Sonic hedgehog. The expression of Sonic hedgehog and Fgf-4 is coordinately regulated by a positive feedback loop operating between the posterior mesoderm and the overlying AER. Taken together, these data provide a basis for understanding the integration of growth and patterning in the developing limb.

Animals↗

Temperature-dependent sex determination in the leopard gecko, Eublepharis macularius.

The leopard gecko, Eublepharis macularius, has temperature-dependent sex determination (TSD). Previous reports have shown that females are produced predominantly at cool incubation temperatures and males are produced predominantly at warm incubation temperatures (Pattern Ib). We report here that incubation at even higher temperatures (34 and 35 degrees C) produces mostly females (Pattern II). The lethal maximum constant incubation temperature for this species appears to be just above 35 degrees C. Although a previous study indicated that females from a warm incubation temperature (32 degrees C) failed to lay eggs, we found that 12 of 14 mature females incubated at 32.5 degrees C, and 5 of 6 mature females incubated at 34 degrees C produced fertile eggs and viable hatchlings.

Animals↗

Strategies of mold control in dairy feeds.

Mold growth can occur in dairy feeds only when nutrients are available, correct temperatures exist, oxygen is present, and unbound water is available. Because elimination of any one of these four factors prevents mold growth, management of feed that accounts for these elements is essential. Use of multiple ingredient mold inhibitors recently has become another tool for affecting successful microbiological control of feed.

Animal Feed↗

Research note: the effect of organic acids on Salmonella contamination originating from mouse fecal pellets.

Laboratory mice were inoculated with a nalidixic acid and novobiocin-resistant strain of Salmonella typhimurium. Contaminated fecal pellets were harvested 2 days postinoculation. Each half of a fecal pellet was found to contain equal numbers of Salmonella on a per weight basis. When separate halves were placed into a poultry feed, either treated or untreated, with an organic acid mixture (SAL CURB), the treatment was able to significantly (P < .001) reduce Salmonella contamination of the feed by almost two log orders per gram when compared with the untreated control.

Acetates↗

Incidence of molds and mycotoxins in commercial animal feed mills in seven midwestern states, 1988-1989.

A total of 82 feed manufacturers located within seven midwestern states (Iowa, Nebraska, Minnesota, Illinois, Indiana, Ohio, Michigan) participated in a survey of mold and mycotoxin contamination of corn. Samples were submitted from a composite of the grading samples taken from each incoming load of corn. The survey was initiated in July 1988. During the 12-mo period, moisture content of the corn samples upon receipt at the laboratory ranged from 10.5 to 13.3%. The greatest variation occurred in the springtime. Iowa's corn samples were driest (11.2%), and samples submitted from Ohio were wettest (12.8%). Mold counts averaged 2.63 x 10(4) per gram during the year. The predominant mold found was Fusarium sp. Samples were checked by black light and averaged 25.4% positive during the period. When assayed for mycotoxins, 19.5% of the samples were positive for at least one of the following: aflatoxin, zearalenone, T2 toxin and deoxynivalenol (vomitoxin). Aflatoxin and T2 toxin made up the majority of these samples containing toxin. The highest incidence of mycotoxin-contaminated corn (48%) occurred in samples submitted in July of 1988. Over the 12-mo period, the highest mycotoxin contamination occurred in Iowa, Illinois and Michigan. When samples were subjected to 90% relative humidity and 32 degrees C, an average of 3.9 d was required for mold growth to appear. After incubation, 24.7% of the samples contained one of the four toxins. The data indicate that mold and mycotoxin contamination of mixed samples of corn is widespread, even in the midwestern corn belt of the U.S.

Aflatoxins↗

Use of a most probable number method modified with a deoxyribonucleic probe to monitor control by food preservatives of natural Salmonella contamination in animal meat meals.

A most probable number (MPN) technique using a DNA probe was developed for determination of Salmonella in naturally contaminated meat meals. The method eliminated the need for 180 selective plates and 75 selective tubes and saved 27 h when compared with a traditional technique; yet it still yielded identical MPN of Salmonella per 100 g in five naturally contaminated samples. The method was used to monitor the effect of a commercial food preservative (Sal Curb) at 0, .25, .50, 1.0, and 2.0% in meat meals with initial contaminations of 1,100, 93, or 7 MPN organisms/100 g. The preservative greatly reduced MPN in the 1,100 and 93 MPN samples in a time and dose-dependent manner, but in the sample with 7 MPN organisms/100 g of material, it resulted in 0 MPN organisms per 100 g after 24 h at all levels tested.

Animal Feed↗

A system for involving patients in program planning.

Although standards exist that require occupational therapists and other health care professionals to include patients in the treatment planning process, our observations lead us to believe that patient involvement is not being maximized. The Patient Participation System allows therapists to actively involve patients in a systematic goal-setting process. The initial results of the use of this system indicate that patients can be effectively involved in establishing personalized, specific goals; identifying outcomes; and evaluating treatment effectiveness.

Adult↗