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Biomedical subjects

J B Green

Publications and source records attributed to J B Green.

At least 37 records · Page 2Linked to original sources

Differential effects on Xenopus development of interference with type IIA and type IIB activin receptors.

One candidate for a mesoderm-inducing factor in early amphibian development is activin, a member of the TGF beta family. Overexpression of a truncated form of an activin receptor Type IIB abolishes activin responsiveness and mesoderm formation in vivo. The Xenopus Type IIA activin receptor XSTK9 differs from the Type IIB receptor by 43 and 25% in extracellular and intracellular domains respectively, suggesting the possibility of different functions in vivo. In this paper, we compare the Type IIA receptor with the Type IIB to test such a possibility. Simple overexpression of the wild-type receptors reveals minimal differences, but experiments with dominant negative mutants of each receptor show qualitatively distinct effects. We show that while truncated (kinase domain-deleted) Type IIB receptors cause axial defects as previously described, truncated type IIA receptors cause formation of secondary axes, similar to those seen by overexpression of truncated receptors for BMP-4, another TGF beta family member. Furthermore, in animal cap assays, truncated type IIB receptors inhibit induction of all mesodermal markers tested, while truncated type IIA receptors suppress induction only of ventral markers; the anterior/dorsal marker goosecoid is virtually unaffected. The suppression of ventral development by the type IIA truncated receptor suggests either that the truncated Type IIA receptor interferes with ventral BMP pathways, or that activin signaling through the Type IIA receptor is necessary for ventral patterning.

Activin Receptors↗

Scanning probe microscopy.

During the past year, scanning probe microscopy, especially atomic force microscopy (AFM), has taken root in the biological sciences community, as is evident from the large number of publications and from the variety of specialized journals in which these papers appear. Furthermore, there is a strong indication that the technique is evolving from a qualitative imaging tool to a probe of the critical dimensions and properties of biomolecules and living cells. The next stage of the evolution involves the development of microinstruments for process control and sensing applications. Recent advances have been reported in AFM instrumentation and method. For example, the tapping mode of operation is becoming the method of choice to image biological molecules; work to extend tapping-mode operation in liquids has been reported. Biological molecules can also be imaged at low temperature in a cryo-AFM with improved resolution. The measurement of recognition forces between individual molecules continues to attract much attention and has spawned new concepts for ultra-sensitive biosensors. The AFM is being used increasingly for property measurements such as determining the viscoelastic properties of biological molecules. Finally, structural studies using the AFM abound. Some specific highlights include the mapping of DNA using restriction enzymes, imaging during DNA transcription and determining the mode of drug binding to DNA.

Cell Membrane↗

The P1 component of the middle latency auditory potential may differentiate a brainstem subgroup of Alzheimer disease.

The P1 component of the middle latency auditory evoked potential (MLAEP) was found to be absent in 47.5% of 101 patients with Alzheimer disease (AD). Lack of a P1 component recently has been associated with a more rapid decline in cognitive performance. The blink reflex (BR) was tested in 36 patients with probable AD and 17 elderly control subjects. All subjects also underwent P1 recording. Patients lacking a P1 potential showed a significant increase in latency of the contralateral R2 response of the BR. The P1 component and the R2 response may differentiate a subgroup of AD patients with involvement of the brainstem, especially the reticular formation.

Adult↗

Reading epilepsy.

Explore the source record for details and available documents.

Epilepsy↗

RNA folding.

The number of known motifs for RNA folding and RNA tertiary organization is expanding rapidly as we learn more about the diverse biological functions of RNA. Problems in protein and RNA folding have melded in recent investigations of ribonucleoprotein folding. Theoretical and experimental models are rapidly being developed for the pathways and stabilizing forces involved in RNA folding.

Animals↗

The P1 component of the middle latency auditory evoked potential predicts a practice effect during clinical trials in Alzheimer's disease.

Thirty-five patients with probable Alzheimer's disease who were enrolled in an experimental drug trial of linopirdine underwent repeated testing that included recording the middle latency auditory evoked potential (MLAEP), the Mini-Mental State Examination (MMSE), and the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCOG). Patients lacking the P1 component of the MLAEP exhibited a significantly greater decline in cognitive function as measured by the ADASCOG over 56 weeks. This decline appeared to be due to a less robust practice effect, which was maximal in all patients at 16 weeks. At the end of 56 weeks the entire group of patients was near baseline with respect to the ADASCOG. This lack of the annualized decline expected from other longitudinal studies may be explained by practice and placebo effects. The MMSE did not exhibit a practice effect and showed the expected decline in scores.

Aged↗

Building a kinetic framework for group II intron ribozyme activity: quantitation of interdomain binding and reaction rate.

Ribozyme kinetics and binding studies of a two-piece group II intron were used to mechanistically characterize a reaction analogous to the first step of RNA splicing. Domain 5 RNA (D5) catalyzes specific hydrolysis of an RNA substrate (exD123) composed of sequences surrounding the 5' exon/intron boundary. Both single- and multiple-turnover kinetic analyses produced similar values of kcat (0.04 and 0.1 min-1, respectively) and Km (270 and 190 nM, respectively) for 5' splice site hydrolysis catalyzed by D5. Base pairing is not believed to stabilize the binding of D5 to exD123, so the low Km values suggest that unusual tertiary interactions provide considerable energetic stabilization to this complex. The strength of D5-exD123 binding was confirmed using a new direct binding assay based on gel filtration chromatography. In this initial application of the assay, which systematically underestimates binding by approximately 3-fold, Kd values were obtained in relative agreement with Km. This agreement, together with agreement between kinetically determined variables, suggests that the reaction is described by a straightforward Michaelis-Menten mechanism and that kcat is the rate of the chemical step. This is supported by the log/linear pH/rate profile for kcat which has a slope = 1 up to pH 6.2, consistent with a form of general base catalysis within this linear range. The shape of the plot suggests that the active site responsible for 5' splice site hydrolysis has a pKa of > or = 7.0.

Base Sequence↗

Borrowing thy neighbour's genetics: neural induction and a Brachyury mutant in Xenopus.

A recent article by Rao exemplifies a number of new trends in developmental biology, both of technical strategy and approach to the problem of neural induction. Rao introduced into frog embryos a mutant form of a mesodermal gene, Brachyury, and caused ectopic neural differentiation. This essay traces the route from the original Brachyury mutation in mouse to the most likely conclusion of Rao's experiments--suggested previously--that neural fate is a default pathway.

Animals↗

Vitamin A intake and status influence retinol balance, utilization and dynamics in rats.

To study effects of vitamin A status on retinol dynamics, male rats were fed purified diets varying in vitamin A concentration. Group 1 rats had marginal liver vitamin A levels (approximately 500 nmol) and were in a slight positive vitamin A balance; Group 2 had similar liver levels but were in a slight negative balance; Group 3 had lower liver levels (approximately 370 nmol) and were in a slight negative balance; Group 4 had depleted liver reserves (<10 nmol) and were in vitamin A balance. [3H]Retinol-labeled plasma was injected intravenously, and serial plasma samples were collected for 41 d while rats (six per group) consumed approximately 50 nmol retinol/d (Group 1) or -25 nmol/d (Groups 2-4). Plasma retinol was normal in Groups 1-3 (1.9-2.0 micromol/L) and lower in Group 4 (0.96 micromol/L). Plasma tracer data were fit to a three-compartment model. The central plasma retinol compartment (transit time, 1.5-1.7 h) exchanged with a fast turning-over extravascular vitamin A pool (transit time, 3-4.5 h; -40 nmol) and with a larger, slow turning-over extravascular pool (transit time, 5.5-10 d) that was the site of irreversible utilization of vitamin A. Irreversible utilization was 36 nmol/d (Group 1), 29 nmol/d (Groups 2 and 3) and 20 nmol/d (Group 4). The data indicate that in rats with low or marginal vitamin A status, vitamin A intake, vitamin A reserves and plasma retinol concentration all influence vitamin A utilization and other aspects of retinol dynamics.

Animals↗

Slow emergence of a multithreshold response to activin requires cell-contact-dependent sharpening but not prepattern.

The growth factor activin elicits mesodermal fates when applied to prospective ectodermal cells of the Xenopus blastula stage embryo. Previous experiments with dissociated cells showed that there are at least five different responses separated by closely spaced, sharp dose thresholds. Here we investigate this multithreshold activin response further using probes for genes expressed at early gastrula stages, namely Xbra, goosecoid, noggin, Xwnt-8 and Mix.1. We show that initial dose-response profiles are broad and smooth in contrast to the later threshold-bound patterns. For Xbra, goosecoid and noggin, the later expression ranges are subsets of earlier ones. Unexpectedly, Xwnt-8 is initially induced at high doses only, but later appears only in cells that have received a low dose of activin. Keeping the cells dissociated after activin treatment, rather than allowing them to reaggregate, prevents sustained expression of Xbra and Xwnt-8 but allows that of goosecoid and noggin. However, cell contact is required for sharpening the dose-response threshold of goosecoid. Finally, we show that a previously reported dorsoventral prepattern in the animal cap is also cell-contact dependent and it is not required for the multi-threshold response to activin.

Activins↗

Intercellular signalling in mesoderm formation during amphibian development.

The mesoderm of amphibian embryos arises through an inductive interaction in which a signal from the vegetal hemisphere of the blastula-stage embryo acts on overlying equatorial cells. Strong candidates for endogenous mesoderm-inducing signals include members of the fibroblast growth factor (FGF) and activin families. In this paper we show that cells form different mesodermal cell types in response to different concentrations of these factors, and that graded distributions of activin and FGF can, in principle, provide sufficient positional information to generate the body plan of the Xenopus embryo.

Activin Receptors↗

Mucinous carcinoma--just another colon cancer?

The significance of mucinous carcinoma has been controversial since first described by Parham in 1923. Previous reports have suggested that mucinous tumors affect young patients, involve the more proximal colon, are more advanced at diagnosis, and have a poorer prognosis than nonmucinous colon carcinoma. More recent reports have refuted these results. In an effort to clarify the significance of mucinous histology, a retrospective review of cases of invasive colon cancer treated at the Ochsner Clinic between 1982 and 1985 was undertaken. Mucinous adenocarcinoma, as defined by > or = 50 percent mucin, was found in 52 patients. During the same period, 343 nonmucinous adenocarcinomas were resected. The mean age, distribution within the colon, stage at diagnosis, and survival of mucinous carcinoma patients were compared with those with nonmucinous tumors. Mucinous tumors presented at a statistically significant more advanced stage (38 percent vs. 22 percent Dukes C lesions; P < 0.01). No significant differences were seen in age at presentation, distribution within the colon, or stage-for-stage survival when the entire group was analyzed. Mucinous carcinomas of the rectum occurred at an advanced stage more frequently (P < 0.05) than nonmucinous rectal carcinomas and had a markedly worse five-year survival (11 percent vs. 57 percent; P < 0.002).

Actuarial Analysis↗