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S Schultz

Publications and source records attributed to S Schultz.

At least 55 records · Page 3Linked to original sources
PubMed1999

On decoding the responses of a population of neurons from short time windows.

The effectiveness of various stimulus identification (decoding) procedures for extracting the information carried by the responses of a population of neurons to a set of repeatedly presented stimuli is studied analytically, in the limit of short time windows. It is shown that in this limit, the entire information content of the responses can sometimes be decoded, and when this is not the case, the lost information is quantified. In particular, the mutual information extracted by taking into account only the most likely stimulus in each trial turns out to be, if not equal, much closer to the true value than that calculated from all the probabilities that each of the possible stimuli in the set was the actual one. The relation between the mutual information extracted by decoding and the percentage of correct stimulus decodings is also derived analytically in the same limit, showing that the metric content index can be estimated reliably from a few cells recorded from brief periods. Computer simulations as well as the activity of real neurons recorded in the primate hippocampus serve to confirm these results and illustrate the utility and limitations of the approach.

Algorithms↗
PubMed1999

Development and implementation of a clinical pathway for patients undergoing total laryngectomy: impact on cost and quality of care.

BACKGROUND: The current health care climate demands the provision of quality patient care in a cost-effective manner. Clinical pathways define the essential components of care that are provided to patients with a specific diagnosis to achieve a desired outcome within a predetermined period. Development and implementation of clinical pathways streamline the provision of quality care in the most cost-effective manner. OBJECTIVES: To develop a clinical pathway for patients undergoing total laryngectomy and to evaluate its impact on the cost and quality of care provided to these patients. SETTING: A tertiary care academic medical center. PATIENTS AND METHODS: A total of 45 patients were included in the study. The clinical pathway was implemented for 15 patients, while the other 30 patients were treated without the implementation of the pathway guidelines. MAIN OUTCOME MEASURES: Length of hospital stay, readmission rate, and hospital variable costs. RESULTS: The clinical pathway affected all cost outcome measures. Length of stay decreased by 2.4 days (29%; P=.001), and the average hospital variable cost decreased from $3992 to $3419 per case. This represents a 14.4% reduction in cost associated with pathway implementation (P=.02). The standardization of care eliminated unnecessary variation and repetition in resource usage, resulting in overall cost reduction. Pathway implementation resulted in a lower readmission rate (7% [1/15]) than that of patients treated prior to protocol implementation (23% [7/30]). CONCLUSION: Implementing a carefully developed clinical pathway may reduce cost without compromising the quality of care for patients undergoing total laryngectomy.

Cost Control↗
PubMed1999

Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase.

Pyruvate formate-lyase (PFL) from Escherichia coli uses a radical mechanism to reversibly cleave the C1-C2 bond of pyruvate using the Gly 734 radical and two cysteine residues (Cys 418, Cys 419). We have determined by X-ray crystallography the structures of PFL (non-radical form), its complex with the substrate analog oxamate, and the C418A,C419A double mutant. The atomic model (a dimer of 759-residue monomers) comprises a 10-stranded beta/alpha barrel assembled in an antiparallel manner from two parallel five-stranded beta-sheets; this architecture resembles that of ribonucleotide reductases. Gly 734 and Cys 419, positioned at the tips of opposing hairpin loops, meet in the apolar barrel center (Calpha-Sgamma = 3.7 A). Oxamate fits into a compact pocket where C2 is juxtaposed with Cys 418Sgamma (3.3 A), which in turn is close to Cys 419Sgamma (3.7 A). Our model of the active site is suggestive of a snapshot of the catalytic cycle, when the pyruvate-carbonyl awaits attack by the Cys 418 thiyl radical. We propose a homolytic radical mechanism for PFL that involves Cys 418 and Cys 419 both as thiyl radicals, with distinct chemical functions.

Acetyltransferases↗
PubMed1998

The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells.

The role of hematopoietic growth factors in lineage commitment and differentiation is unclear. We present evidence that heterologous expression of an erythroid specific receptor allows granulocytic differentiation of a myeloid cell line. We have previously characterized a truncation mutant of the erythropoietin receptor (EpoR), which is associated with familial erythrocytosis (Blood 89:4628, 1997). This truncated EpoR lacks the distal 70 amino acids of the cytoplasmic domain. To study the functional role of this distal receptor domain, 32D cells, a murine interleukin-3 (IL-3)-dependent myeloid line, were transfected with the wild-type EpoR (32D/EpoR WT) or the truncated EpoR (32D/EpoR FE). 32D cells expressing either the full-length or truncated EpoR display equivalent proliferative rates in saturating concentrations of Epo. There is a dramatic difference in maturational phenotype between the two cell lines, however. The 32D/EpoR FE cells and mock transfected 32D cells have an immature, monoblastic morphology and do not express the primary granule protein myeloperoxidase. The 32D/EpoR WT cells, on the other hand, demonstrate granulocytic differentiation with profuse granulation, mature, clumped chromatin, and myeloperoxidase expression. There is no evidence of erythroid differentiation in 32D cells transfected with either the full-length or truncated EpoR. Treatment of the cells with the specific Jak2 inhibitor tyrphostin AG 490 inhibits myeloid differentiation driven by the distal EpoR. We conclude that: (1) the distal cytoplasmic domain of the EpoR is able to induce a specific myeloid differentiation signal distinct from mitogenic signaling, and (2) these data extend to myelopoiesis the growing body of evidence that the cellular milieu, not the specific cytokine receptor, determines the specificity of differentiation after cytokine receptor activation.

Animals↗
PubMed1998

Isolation and crystallization of functionally competent Escherichia coli peptide deformylase forms containing either iron or nickel in the active site.

Three metallo forms of peptide deformylase (PDF, EC 3.5.1.31) of Escherichia coli were prepared and crystallized (space group C2, diffraction limit 1.9 A) for initiating the X-ray structure determination of the metal center in correlation with the catalytic functionality of this enzyme. The native Fe2+ containing enzyme species was directly isolated from overproducing bacteria by using catalase as a buffer additive, which stabilizes the catalytic activity against oxidative destruction. The Ni2+ containing form, which is oxygen-insensitive, was obtained by metal exchange with free Ni2+ and found to be catalytically equally effective (kcat/KM = 10(5) M-1 s-1 for N-formyl-Met-Ala). The Zn2+ form, prepared from the apoenzyme or by displacement of bound Ni2+ by free Zn2+, proved virtually inactive.

Amidohydrolases↗
PubMed1998

Structure of peptide deformylase and identification of the substrate binding site.

Peptide deformylase is an essential metalloenzyme required for the removal of the formyl group at the N terminus of nascent polypeptide chains in eubacteria. The Escherichia coli enzyme uses Fe2+ and nearly retains its activity on substitution of the metal ion by Ni2+. We have solved the structure of the Ni2+ enzyme at 1.9-A resolution by x-ray crystallography. Each of the three monomers in the asymmetric unit contains one Ni2+ ion and, in close proximity, one molecule of polyethylene glycol. Polyethylene glycol is shown to be a competitive inhibitor with a KI value of 6 mM with respect to formylmethionine under conditions similar to those used for crystallization. We have also solved the structure of the inhibitor-free enzyme at 2.5-A resolution. The two structures are identical within the estimated errors of the models. The hydrogen bond network stabilizing the active site involves nearly all conserved amino acid residues and well defined water molecules, one of which ligates to the tetrahedrally coordinated Ni2+ ion.

Amidohydrolases↗
PubMed1998

Position-related changes in voiding dynamics in men.

OBJECTIVES: To investigate by urodynamic study position-related changes in uroflowmetry and postvoid residual urine volume (PVR) in men because altered bladder function in the supine position may be a predisposing factor for urinary tract infections in the institutionalized elderly. METHODS: Two healthy men, 34 and 59 years of age and living at home, and 53 nursing home residents (mean age 71.8 years, range 46 to 92) were evaluated with uroflowmetry in the standing and recumbent positions (lying on the left or right side); corresponding PVRs were measured by transabdominal ultrasonic bladder scanning. The two healthy men were monitored longitudinally with multiple recordings in both voiding positions, and the nursing home residents were subjected to two observations: one measurement of the variable parameters in either position. Differences were considered to be significant at P < 0.05. RESULTS: The 34-year-old man performed 51 3 flows (368 standing and 145 recumbent). The mean of all the peak flow rates in the upright (28.2 +/- 4.2 mL/s) versus the recumbent (16.8 +/- 4.1 mL/s) position revealed a highly significant difference (P = 0.0001). Sixteen urinary flows and corresponding PVRs were completed by this subject in either voiding position. The difference between PVRs in the standing (13.1 +/- 14.7 mL) versus recumbent (15.3 +/- 17.5 mL) position was not statistically significant. The 59-year-old man completed 156 flows (128 standing and 28 recumbent). A highly significant difference was noted between the mean of all peak flows in the upright (18.9 +/- 4.1 mL/s) versus recumbent (12.6 +/- 2.0 mL/s) position (P = 0.0001). Thirty-seven urinary flows and corresponding PVRs were completed by this individual (10 PVRs were determined after voiding in the standing and 27 after voiding in the recumbent position). No significant difference was noted between PVRs in the standing (24.6 +/- 34.4 mL) versus recumbent (16.5 +/- 60.0 mL) position. In the nursing home residents, the difference between the mean peak flow rates in the standing (14.5 +/- 8.6 mL/s) versus recumbent (12.4 +/- 6.7 mL/s) position also reached statistical significance (P = 0.0084). The difference between PVRs in the standing (60.5 +/- 125.6 mL) versus recumbent (84.8 +/- 186.2 mL) position barely reached statistical significance (P = 0.0497). CONCLUSIONS: The urinary flow rate decreases in the recumbent position. Bedridden residents may be predisposed to urinary tract infections because of alterations in voiding dynamics in the supine position. This area needs further study.

Adult↗