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Biomedical subjects

M L Walker

Publications and source records attributed to M L Walker.

126 records · Page 7Linked to original sources

A second generation apparatus for time-resolved electron cryo-microscopy using stepper motors and electrospray.

We describe here a second generation apparatus for studying transient reaction conformations in macromolecules and their complexes by electron cryo-microscopy. Reactions are trapped by rapid freezing in times ranging from a few milliseconds to tens of seconds after initiation. Blotting of the electron microscope grid and freezing it in liquid ethane uses computer controlled microstepping motors. For the fastest time resolution, a blotted grid containing a thin film of one reactant is sprayed with small droplets containing a second reactant just before freezing. The spray is produced electrically (electrospray), which gives a dense cloud of droplets <1 microm in diameter from the 1-2 microl of solution required per grid. A second method in which two solutions are first mixed by turbulent flow and then blotted prior to freezing is used for reactions with time courses >1s.

Biophysical Phenomena↗

The structure of dynein-c by negative stain electron microscopy.

Dynein ATPases contain six concatenated AAA modules within the motor region of their heavy chains. Additional regions of sequence are required to form a functional ATPase, which a previous study suggested forms seven or eight subdomains arranged in either a ring or hollow sphere. A more recent homology model of the six AAA modules suggests that these form a ring. Therefore both the number and arrangement of subdomains remain uncertain. We show two-dimensional projection images of dynein-c in negative stain which reveal new details of its structure. Initial electron cryomicroscopy shows a similar overall morphology. The molecule consists of three domains: stem, head, and stalk. In the absence of nucleotide the head has seven lobes of density forming an asymmetric ring. An eighth lobe protrudes from one side of this heptameric ring and appears to join the elongated cargo-binding stem. The proximal stem is flexible, as is the stalk, suggesting that they act as compliant elements within the motor. A new analysis of pre- and post-power stroke conformations shows the combined effect of their flexibility on the spatial distribution of the microtubule-binding domain and therefore the potential range of power stroke sizes. We present and compare two alternative models of the structure of dynein.

Animals↗

Eating disorders with and without substance use disorders: a comparative study of inpatients.

We assessed the co-occurrence of DSM-III-R axis I and II disorders and self-reported psychologic distress in inpatients with eating disorders with and without substance use disorders (ED-SUD and ED groups, respectively) and in a matched comparison sample with substance use disorders but no eating disorder (SUD group). The three groups showed similar distributions of axis I disorders but differed in the distribution of axis II disorders. Cluster B personality disorders were diagnosed more frequently in SUD and ED-SUD groups than in the ED group. In contrast, cluster C personality disorders were diagnosed more frequently in the ED group than in SUD and ED-SUD groups. The SUD group reported greater psychologic distress than ED and ED-SUD groups. Possible implications of the observed group differences for psychologic models of why these disorders may be associated are considered.

Adolescent↗

Diagnostic comorbidity in hospitalized adolescents with conduct disorder.

We compared the diagnostic comorbidity of DSM-III-R axis I and axis II disorders in a sample of hospitalized adolescents with conduct disorder (CD) and a comparison group of hospitalized adolescents without conduct disorder (non-CD). Of 138 consecutively evaluated adolescents, 76 patients met criteria for CD and 62 did not. On axis I, CD was significantly comorbid with attention-deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs). None of the personality disorders assessed showed differential association with CD. The comorbid relationships found within this sample suggest a strong association between CD, ADHD, and SUD in hospitalized teenagers. This finding underscores the clinical importance of conducting a thorough developmental assessment and, when indicated, of treating ADHD and SUD in conduct-disordered adolescents.

Adolescent↗

Psychiatric comorbidity differences in male and female adult psychiatric inpatients with substance use disorders.

To examine gender differences in the co-occurrence of DSM-III-R axis I disorders and axis II personality disorders in young adult psychiatric inpatients with substance use disorders (SUDs), a consecutive series of 70 inpatients (33 men and 37 women) with SUD were reliably assessed with structured diagnostic interviews. Higher rates of dysthymia and eating disorders were observed in SUD females and higher rates of cluster A personality disorders were observed in SUD males. No gender differences were found for depression or anxiety in our SUD inpatients; these findings contrast with gender ratios for these disorders in the general population. In conclusion, relatively few gender differences were found in young adult inpatients with SUD, even where they would be expected based on general population gender patterns.

Adolescent↗

Lasers in pediatric neurosurgery.

The carbon dioxide (CO2) laser is a microsurgical instrument to be used in conjunction with good neurosurgical technique. Laser surgery has special applications in pediatric neurosurgery because of the type and location of many pediatric tumors as well as the laser qualities of precision and decreased tissue trauma. The CO2 laser has proven to be a valuable surgical tool in this series of pediatric spinal cord and brain tumor patients. The areas of most effective laser treatment were the posterior fossa, ventricles, spinal cord and the suprasellar area. The laser was least helpful in tumors of the hemispheres and the hypothalamus. Criteria need to be developed for absolute and relative indications for CO2 laser use.

Adolescent↗

Intraoperative monitoring in selective dorsal rhizotomy.

The method used in the intraoperative portion of the selective dorsal rhizotomy procedure for the selection of abnormal circuits within the central nervous system of children with spasticity due to cerebral palsy is described. The decision to transect dorsal rootlets is made on the basis of electrophysiological, behavioral and medical criteria. In 100 cases the average number of rootlets transected was 64%. Of the total stimulated, 23.3% exhibited normal electrophysiological and behavioral responses. Decision making regarding the preservation or transection of the remaining 12.7% of the segments is described. This information is presented in an effort to increase understanding of this particular portion of the procedure and to encourage standardization of the procedure between centers in the future.

Child↗

An environmental threshold for degree of phosphorus saturation in sandy soils.

There is critical need for a practical indicator to assess the potential for phosphorus (P) movement from a given site to surface waters, either via surface runoff or subsurface drainage. The degree of phosphorus saturation (DPS), which relates a measure of P already adsorbed by a soil to its P adsorption capacity, could be a good indicator of that soil's P release capability. Our primary objective was to find a suitable analytical protocol for determining DPS and to examine the possibility of defining a threshold DPS value for Florida's sandy soils. Four farmer-owned dairy sprayfields were selected within the Suwannee River basin and soil profiles were randomly obtained from each site, as well as from adjacent unimpacted sites. The soil samples were divided either by horizon or depth, and DPS was determined for each soil sample using ammonium-oxalate (DPS(Ox)), Mehlich-1 (DPS(M1)), and Mehlich-3 (DPS(M3)) extracts. All methods of DPS calculations were linearly related to one another (r2 > 0.94). Relationships between water-soluble P and DPS indicate that the respective change points are: DPS(Ox) = 20%, DPS(M1) = 20%, and DPS(M3) = 16%. These relationships include samples from Ap, E, and Bt horizons, and various combinations thereof, suggesting that DPS values can be used as predictors of P loss from a soil irrespective of the depth of the soil within a profile. Taking into consideration the change points, confidence intervals, agronomic soil test values, and DPS values from other studies, we suggest replacing Mehlich-1 P values in the Florida P Index with the three DPS categories (DPS(M1) = <30, 30-60, and >60%) to assign different P loss ratings in the P Index.

Animals↗

Cerebral trauma-induced changes in corpus striatal dopamine receptor subtypes.

A device designed specifically for mild to severe concussions was used to produce quantitative experimental blunt brain injury in male Wistar rats. We have examined the effects of varying magnitudes of cerebral trauma on the maximal binding capacity (Bmax) of D1 and D2 dopamine (DA) receptors. The Bmax for each receptor subtype was obtained from Scatchard analyses of [3H]-SCH 23390 and [3H]Spiperone binding to striatal membrane. Anesthetized rats were injured--one, two, or three times--once every 24 h, with either a 68- or 268-g rubber-headed reflex hammer accelerated from a predetermined distance. Uninjured nonanesthetized (NA) and anesthetized (A) rats served as controls. No significant difference in receptor density was observed between NA and A rats for each receptor subtype. Immediately (0 h) following injury from the 68-g hammer weight, the density of D1 receptors decreased (50%), then increased (30%) above control levels by 24 h. The same pattern was observed with the 268-g hammer weight. Analysis of variance (ANOVA) showed that there was no overall effect of number of injuries or treatment on the density of D1 and D2 receptor subtypes. However, there was an interaction of both variables on the D1, but not D2, receptor subtype. Partial ANOVA for receptor densities after rats were injured either one, two, or three times showed that receptor density was altered only after the rats were injured one time. These results suggest that striatal DA D1 receptors are downregulated and then upregulated following isolated injury to the cerebral cortex.

Animals↗

Drug misuse.

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Aged↗