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Biomedical subjects

G Rosenbaum

Publications and source records attributed to G Rosenbaum.

At least 19 recordsLinked to original sources

The BioCAT undulator beamline 18ID: a facility for biological non-crystalline diffraction and X-ray absorption spectroscopy at the Advanced Photon Source.

The 18ID undulator beamline of the Biophysics Collaborative Access Team at the Advanced Photon Source, Argonne, IL, USA, is a high-performance instrument designed for, and dedicated to, the study of partially ordered and disordered biological materials using the techniques of small-angle X-ray scattering, fiber diffraction, and X-ray absorption spectroscopy. The beamline and associated instrumentation are described in detail and examples of the representative experimental results are presented.

Academies and Institutes↗

Design of a vacuum-compatible high-precision monochromatic beam-position monitor for use with synchrotron radiation from 5 to 25 keV.

The Structural Biology Center beamline, 19ID, has been designed to take full advantage of the highly intense undulator radiation and very low source emittance available at the Advanced Photon Source. In order to keep the X-ray beam focused onto the pre-sample slits, a novel position-sensitive PIN diode array has been developed. The array consists of four PIN diodes positioned upstream of a 0.5 microm-thick metal foil placed in the X-ray beam. Using conventional difference-over-the-sum techniques, two-dimensional position information is obtained from the metal foil fluorescence. Because the full X-ray beam passes through the metal foil, the true beam center-of-mass is measured. The device is compact, inexpensive to construct, operates in a vacuum and has a working range of 8 mm x 10 mm that can be expanded with design modifications. Measured position sensitivity is 1-2 microm. Although optimized for use in the 5-25 keV energy range, the upper limit can be extended by changing metals or adjusting foil thickness.

Journal Article↗

[Application of a preoperative evaluation model in patients undergoing elective abdominal surgery].

We used a preoperative evaluation model based on the clinical history in order to determine the clinical characteristics of the patients. We also estimated the prevalence of asymptomatic disease in ASA1 patients and described the frequency of diagnosis that motivated suspension of the surgery during the preoperative time. Another purpose was to establish the perioperative complications according to the risk index and to detect the medical reasons for suspension of surgery during hospitalization. A total of 777 patients having an indication of surgery were evaluated in this program. Only 507 completed the preoperative evaluation. Of these, 57.79%, had at least one known disease or were diagnosed by their clinical history. Preoperative tests were indicated according to age in ASA1 patients. Complementary studies were indicated in relationship to the history and physical examination in ASA2 and ASA3 patients. After the evaluation, 27 surgeries were suspended: 21 were considered high risk, 2 suffered unknown active infections, and 4 ASA1 patients had severe asymptomatic anemia. A total of 328 patients were admitted for surgery. In 5 of these patients the anesthesiologist stopped the procedure in the operating room. The causes were acute decompensations of known pathologies. There were no complications or deaths related to unknown diseases and no patients died from cardiopulmonary or metabolic complications. In ASA1 patients, there were no complications related to this evaluation. This study allowed us to determine the clinical status of the patients and in consequence high-risk surgeries were canceled. In admitted patients a few surgeries were canceled for clinical reasons. This program probably decreased patient morbimortality, unnecessary hospitalization and costs.

Adolescent↗

The M.ADP.Pi state is required for helical order in the thick filaments of skeletal muscle.

The thick filaments of mammalian and avian skeletal muscle fibers are disordered at low temperature, but become increasingly ordered into an helical structure as the temperature is raised. Wray and colleagues (Schlichting, I., and J. Wray. 1986. J. Muscle Res. Cell Motil. 7:79; Wray, J., R. S. Goody, and K. Holmes. 1986. Adv. Exp. Med. Biol. 226:49-59) interpreted the transition as reflecting a coupling between nucleotide state and global conformation with M.ATP (disordered) being favored at 0 degrees C and M.ADP.P(i) (ordered) at 20 degrees C. However, hitherto this has been limited to a qualitative correlation and the biochemical state of the myosin heads required to obtain the helical array has not been unequivocally identified. In the present study we have critically tested whether the helical arrangement of the myosin heads requires the M.ADP.P(i) state. X-ray diffraction patterns were recorded from skinned rabbit psoas muscle fiber bundles stretched to non-overlap to avoid complications due to interaction with actin. The effect of temperature on the intensities of the myosin-based layer lines and on the phosphate burst of myosin hydrolyzing ATP in solution were examined under closely matched conditions. The results showed that the fraction of myosin mass in the helix closely followed that of the fraction of myosin in the M.ADP.P(i) state. Similar results were found by using a series of nucleoside triphosphates, including CTP and GTP. In addition, fibers treated by N-phenylmaleimide (Barnett, V. A., A. Ehrlich, and M. Schoenberg. 1992. Biophys. J. 61:358-367) so that the myosin was exclusively in the M.ATP state revealed no helical order. Diffraction patterns from muscle fibers in nucleotide-free and in ADP-containing solutions did not show helical structure. All these confirmed that in the presence of nucleotides, the M.NDP.P(i) state is required for helical order. We also found that the spacing of the third meridional reflection of the thick filament is linked to the helical order. The spacing in the ordered M.NDP.P(i) state is 143.4 A, but in the disordered state, it is 144. 2 A. This may be explained by the different interference functions for the myosin heads and the thick filament backbone.

Adenosine Diphosphate↗

Energy-resolving X-ray fluorescence detection using synthetic multilayers.

The potential of synthetic multilayers for energy-resolving the X-ray fluorescence in X-ray absorption fine structure (XAFS) experiments is discussed. Two detection systems, one using curved multilayers and the other using graded multilayers to select X-ray fluorescence photons, have been designed to cover a wide energy range with a usefully large solid angle. Such a detector will be more advantageous than the barrel-like crystal-array detector because of the unique properties of synthetic multilayers, such as larger horizontal acceptance angles and bandwidth. In addition, the detector should be much simpler to construct and readily accommodates energy changes, especially the detector using graded multilayers. Comparison of the multilayer array detector with conventional detectors, such as ionization chambers and conventional 13-element Ge detectors, shows that the proposed system will be superior, particularly with the increased photon fluxes available from insertion devices and with decreased sample concentration, since this detection system eliminates the ;bad' photons before they enter any X-ray detector. Consequently, the X-ray detector proper for this system does not suffer from the incident-count-rate bottleneck common to current X-ray fluorescence detectors with energy resolution by signal processing. Thus, this new fluorescence detection system will provide tremendous opportunities for XAFS measurements on dilute systems, such as biological systems, at third-generation synchrotron sources.

Journal Article↗

How X-ray Diffraction with Synchrotron Radiation Got Started.

The need to record low-angle-scattering X-ray fibre diagrams from muscle with millisecond time resolution drove the use of synchrotron radiation as an X-ray light source. The first smudgy diffraction patterns were obtained from a slice of insect flight muscle. Out of this grew the EMBL Outstation at DESY.

Journal Article↗

Normalizing the crossover effect: enhancement of cognitive attentional processing in schizophrenia.

Thirty male schizophrenic subjects and 20 male control subjects were administered both the classic Rodnick and Shakow reaction time (RT) procedure and a modified experimental procedure using a balanced design in an attempt to enhance cognitive attentional processing and inhibit the crossover effect in schizophrenic patients. The experimental procedure increased the number of predictable trials, provided more information about the task and presented the regular trials in a simple ascending order. Analysis of the RT data showed the typical early schizophrenic crossover and late normal crossover on the standard task, while schizophrenic patients in the experimental condition showed a new finding of statistically significant normalization of the early crossover effect. The results support Shakow's theory of attentional set deficit in schizophrenia and in conjunction with previous findings suggest that separate neuropsychological mechanisms of cognitive preparatory attention and a more automatic form of vigilance attention may, respectively, underlie the regular and irregular procedures of the traditional RT task.

Adolescent↗

MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family.

BACKGROUND: The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. It is expressed from a gene located at a fragile site on human chromosome 3, which is commonly disrupted in association with certain cancers. On the basis of the genetic evidence, it has been postulated that the FHIT protein may function as a tumor suppressor, implying a role for the FHIT protein in carcinogenesis. The FHIT protein has dinucleoside polyphosphate hydrolase activity in vitro, thus suggesting that its role in vivo may involve the hydrolysis of a phosphoanhydride bond. The structural analysis of FHIT will identify critical residues involved in substrate binding and catalysis, and will provide insights into the in vivo function of HIT proteins. RESULTS: The three-dimensional crystal structures of free and nucleoside complexed FHIT have been determined from multiwavelength anomalous diffraction (MAD) data, and they represent some of the first successful structures to be measured with undulator radiation at the Advanced Photon Source. The structures of FHIT reveal that this protein exists as an intimate homodimer, which is based on a core structure observed previously in another human HIT homolog, protein kinase C interacting protein (PKCI), but has distinctive elaborations at both the N and C termini. Conserved residues within the HIT family, which are involved in the interactions of the proteins with nucleoside and phosphate groups, appear to be relevant for the catalytic activity of this protein. CONCLUSIONS: The structure of FHIT, a divergent HIT protein family member, in complex with a nucleotide analog suggests a metal-independent catalytic mechanism for the HIT family of proteins. A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins.

Acid Anhydride Hydrolases↗

Assessment of differential attention mechanisms in seizure disorders and schizophrenia.

This study examines differential attention deficits in 19 temporal lobe epilepsy (TLE) patients, 15 generalized seizure patients (GSP), and 19 schizophrenic patients, compared to 20 normal controls. All participants were tested on a variable foreperiod reaction time (RT) task and continuous performance test (CPT). Temporal lobe epilepsy patients and schizophrenic patients show crossover deficits on the RT task requiring a conscious, effortful, preparatory motor set; while GSP show impairments on the CPT requiring vigilant, self-directed attention to external stimuli. The results suggest separate cortical and subcortical brain systems in the respective attentional deficits and in the etiologies of TLE, GSP, and schizophrenic disorders.

Adult↗

Multiple deficit theory of schizophrenia: incidence of markers vs. symptoms.

Forty schizophrenic, 20 affective-disordered, and 40 matched normal control subjects were compared on postulated marker and symptom measures of schizophrenic deficits in: (a) affect; (b) attention; (c) proprioception; and (d) thought. The schizophrenic group was significantly more impaired on all four vulnerability markers than were the other two groups, while the schizophrenic and affective-psychotic groups showed comparable impairments on three of the psychotic symptom deficits. The incidence of multiple marker deficits was significantly greater in the schizophrenic than in the affective group. The hypothesis of independence of marker deficits was supported by the absence of any significant correlations among markers in the schizophrenic sample. The data support the theory that independent markers of schizophrenic vulnerability may potentiate schizophrenic disorders when their incidence is concurrent and at deficit levels.

Adult↗

An atomic model of the unregulated thin filament obtained by X-ray fiber diffraction on oriented actin-tropomyosin gels.

We present a model of the actin-tropomyosin complex in which the radial and azimuthal position of tropomyosin was adjusted to fit the X-ray fiber diffraction patterns from oriented actin-tropomyosin gels at a resolution of 1/8 A-1. We used the recently published atomic F-actin model for the calculations. The atomic model of tropomyosin was obtained by model-building a coiled coiled-coil structure from the tropomyosin sequence. The resulting atomic model is strongly preferred and shows strong electrostatic interactions between charged side-chains of tropomyosin residues and actin residues in subdomain 3 and subdomain 4. Furthermore, calculations of enthalpies based upon electrostatic interactions indicate that there is a favored rotational position of the tropomyosin core at the calculated azimuthal and radial position given by the X-ray refinement. Rotations of the tropomyosin strand out of this position turn strongly attractive electrostatic interactions into repulsive forces. The resulting binding radius of 39 A and the determined azimuthal position of tropomyosin are in good agreement with electron microscopy reconstructions and neutron diffraction experiments. Furthermore, the calculated position of tropomyosin would still partly block the rigor interaction of myosin cross-bridges with actin, whereas it very likely allows undisturbed binding of the cross-bridges in a weak binding state.

Actins↗

The alcohol paradox: a psychological model.

The paradoxical continuation of excessive drinking by chronic alcoholics despite extremely aversive personal deterioration is addressed by a two-factor theory. The theory regards the increasing stereotypy of alcohol-related behaviors as a function of: (a) primary neuropsychological impairments that result from alcohol abuse and (b) secondary fears of catastrophic failure attendant upon brain dysfunction, which leads to acquired aversions to situations that require adaptive behaviors. A schematic quantitative model of this formulation is presented that may be useful to practicing psychologists in explaining perserverative behavior in a variety of brain syndromes.

Adaptation, Psychological↗

Effect of potassium-induced cortical spreading depression on prostaglandin-induced fever in conscious and urethane-anesthetized rats.

Potassium-induced cortical spreading depression (CSD) on prostaglandin E1 (PGE1) induced fever has been investigated in a dose-responsive experimental design in both conscious and urethane-anesthetized adult male Sprague-Dawley rats. While CSD in itself had no effect on nonfebrile body temperature even under cold ambient conditions, CSD significantly suppressed small but not large fevers induced by intracerebroventricular PGE1. The increased oxygen consumption during fever was also reduced. We also explored the possible involvement of the antipyretic peptide arginine vasopressin, in the CSD-induced suppression of fever. Long term castrated rats have significantly reduced ventral septal levels of this peptide, yet CSD was effective in suppressing the initial 40 min of PGE1 fever in these animals. Thus we conclude that increased release of ventral septal arginine vasopressin is probably not involved in the action of CSD on fever.

Anesthesia↗

Obesity: an indication rather than contraindication to laparoscopic cholecystectomy.

Obesity was originally designated as a contraindication to laparoscopic cholecystectomy; however, as experience in the procedure develops, it is evolving into an indication. Out of the first 325 consecutive patients undergoing laparoscopic cholecystectomy, 91 were determined to be either obese or morbidly obese. Group I (normal body habitus), consisted of 228 patients, group II (obese) 67 patients, and group III (morbidly obese) 24 patients. Six patients were excluded because of inadequate follow-up data. The groups were fairly well matched for age and seemed to differ only in height and weight. Operative time was similar in groups I and II, while it was approximately 23% longer for group III. The outcome of surgery was compared with respect to conversion to open cholecystectomy, postoperative complications, mortality, length of postoperative stay, and return to normal activity. None of the differences were statistically significant with the exception of the slightly longer length of time for laparoscopic cholecystectomy in the morbidly obese. Laparoscopic cholecystectomy is a safe and effective treatment for obese patients and even for morbidly obese patients, and should be the procedure of choice for these patients, avoiding complications of prolonged bedrest and wound complications, so common in these patients.

Journal Article↗

Cognitive and motor deficits in selected unilateral brain-injured patients.

16 right hemisphere and 16 left hemisphere, nonaphasic brain-injured stroke patients were compared with 16 matched normal controls on the verbal and visuospatial paired-associate tasks developed by Stark in 1961 as a partial replication to a more severely impaired population. Right brain-injured patients showed a significant visuospatial deficit and contralateral motor impairment; while left brain-injured patients, screened for aphasia, showed contralateral motor impairment but did not show impairment on the verbal task. Examination of the areas of infarct resulting from the cerebrovascular accident in the left-hemisphere patients suggested that the presence of a contralateral motor deficit without verbal impairment results from specific focal occlusions of branches of the middle cerebral artery in this selective group of patients.

Brain Damage, Chronic↗