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S Schultz

Publications and source records attributed to S Schultz.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Iron center, substrate recognition and mechanism of peptide deformylase.

Eubacterial proteins are synthesized with a formyl group at the N-terminus which is hydrolytically removed from the nascent chain by the mononuclear iron enzyme peptide deformylase. Catalytic efficiency strongly depends on the identity of the bound metal. We have determined by X-ray crystallography the Fe2+, Ni2+ and Zn2+ forms of the Escherichia coli enzyme and a structure in complex with the reaction product Met-Ala-Ser. The structure of the complex, with the tripeptide bound at the active site, suggests detailed models for the mechanism of substrate recognition and catalysis. Differences of the protein structures due to the identity of the bound metal are extremely small and account only for the observation that Zn2+ binds more tightly than Fe2+ or Ni2+. The striking loss of catalytic activity of the Zn2+ form could be caused by its reluctance to change between tetrahedral and five-fold metal coordination believed to occur during catalysis. N-terminal formylation and subsequent deformylation

Amidohydrolases↗
PubMed1996

Effect of background interference on accelerant detection by canines.

Additional studies were performed with respect to examining the lower limits at which canines can reliably detect products commonly used as accelerants and distinguish them from pyrolysis products or background hydrocarbons. As part of a testing exercise performed in conjunction with a national conference of the Canine Accelerant Detection Association (CADA), 34 canines were subjected to a series of tests, some of them were a recertification proficiency. In one of the tests, the dogs were nearly unanimously successful in locating one can (out of five) containing 50% evaporated gasoline at the 5 microL level on a burnt carpet matrix, and pinpointing the 6-in. square sector on a piece of plain carpeting where the same amount of gasoline (5 microL) was applied. However, only half were able to detect a second doped sample containing a lesser amount (0.05, 0.1, or 0.2 microL) of gasoline, and registered a number of alerts on samples containing only burnt carpeting material. The dogs were also tested on measured amounts (2 or 5 microL) of a variety of other light, medium, and heavy petroleum products applied to a variety of substances containing significant pyrolysis products. As a group, the canines were much less successful in pinpointing these products than they were with gasoline at this same level, and again registered a number of alerts on cans containing only pyrolysis products. The significant number of alerts by canines on samples not containing gasoline or other products points out the importance of obtaining laboratory confirmation on samples on which dogs alert, and on keeping accurate field and training records of canines to establish their credibility.

Animals↗
PubMed1995

Identification of nucleotide binding sites in the poliovirus RNA polymerase.

Poliovirus RNA polymerase (3Dpol) was cross-linked to [32P]ribonucleoside triphosphates (NTPs) by reduction of oxidized NTP-protein complexes. Cross-linked complexes were digested with cyanogen bromide, and resulting peptides were fractionated by reverse-phase HPLC. 32P-Labeled peptides were purified by secondary HPLC fractionation and/or additional digestion with endoproteinases Glu-C, TPCK-trypsin, or Asp-N followed by another HPLC fractionation. N-Terminal sequences of the major [32P]-peptides were determined, and approximate sizes of these peptides were obtained by SDS-polyacrylamide gel electrophoresis. Two major NTP binding sites in 3Dpol were found. One site was between Asp-266 and Met-286; possible binding residues in this fragment were Lys-276, Lys-278, or Lys-283. A second binding site was between Ala-57 and Met-74 with Lys-61 or Lys-66 as possible binding residues. Alignment of these regions on the known structure of HIV-1 reverse transcriptase allowed us to predict the position of the downstream nucleotide binding site in the conserved "fingers" subdomain present near the active site cleft of both RNA and DNA polymerases. The N-terminal nucleotide binding site is not contained within a region that is conserved among other polymerases.

Amino Acid Sequence↗
PubMed1995

Signal averaging and waveform analysis of laser Doppler flowmetry monitoring of porcine myocutaneous flaps: I. Acute assessment of flap viability.

Postoperative monitoring of microvascular free-tissue transfer is essential to the early identification and correction of vascular compromise. Laser Doppler flowmetry is a noninvasive monitor of capillary bed perfusion. Its current clinical use requires continuous monitoring and trend analysis to detect changes in capillary perfusion. This study investigated the hypothesis that signal averaging of laser Doppler flowmetry output triggered by a fixed point in the cardiac cycle would provide accurate information about the microvascular flow patterns not dependent on trend analysis. These results indicate that averaged waveform analysis allowed for a rapid, objective, and statistically significant distinction between a viable myocutaneous flap and one with vascular compromise in a porcine model. Moreover, this technique allows for distinction between venous and arterial insufficiency.

Animals↗
PubMed1995

Interventional radiology of the chest: image-guided percutaneous drainage of pleural effusions, lung abscess, and pneumothorax.

Percutaneous catheter drainage of intrathoracic collections has developed as a natural extension of similar interventional radiologic procedures in the abdomen. The advent of CT and sonography, which allow detection and characterization of pleural and parenchymal collections, combined with advances in drainage catheter design and interventional techniques, have made imaging-guided management of intrathoracic collections a safe and effective alternative to traditional surgical therapy. This article begins with a review of the etiology, pathophysiology, diagnosis, and treatment of parapneumonic pleural effusion, which remains the most common indication for image-guided percutaneous drainage. Subsequent sections consider issues related to percutaneous drainage of malignant pleural effusion, lung abscess, and pneumothorax.

Drainage↗
PubMed1994

Pneumonia in a nursing home.

The authors studied nursing home residents serologically to determine whether atypical organisms were causes of radiologic pneumonia. The study was conducted at the Wisconsin Veterans Home, a facility with on-site microbiology and x-ray. Over one year, serologic examinations for Legionella, Mycoplasma, and Chlamydia were conducted for the residents who had pneumonia. Cultures and mortality were reviewed. Fifty-six episodes were studied (mean resident age 78 years). There was no fourfold titer change. Seventeen quality sputum specimens revealed Streptococcus pneumoniae (5), normal flora (4), Hemophilus influenzae (4), Moraxella catarrhalis (3), Staphylococcus aureus (1), and beta-hemolytic Streptococcus, not group A (1). The two-month mortality was 21%. This study did not result in serologic confirmation of atypical organisms' causing pneumonia. Antibiotic choice should be based on coverage of prevalent organisms, including Hemophilus influenzae, Moraxella, and Staphylococcus, as well as clinical features.

Aged↗
PubMed1994

Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men.

OBJECTIVE: It has been proposed that declining activities of the somatotrophic or gonadotrophic axes, or sedentary life style, are partial causes for geriatric losses of bone mineral density (BMD) and of lean body mass (LBM). The present study tested these hypotheses by determining, in both free-living and institutionalized elderly men, the correlations of bone mineral density (BMD), total body bone mineral content (TBBMC) and lean body mass (LBM) with the following predictor variables: age, body mass index, body weight, serum insulin-like growth factor I (IGF-I), serum testosterone, habitual physical activity and mobility. SUBJECTS: Forty-nine independent, community-dwelling older men, and 49 men of similar age residing in two Veterans Administration extended care facilities. The age range was 58-95 years. MEASUREMENTS: Serum IGF-I and testosterone were measured by radioimmunoassay. Habitual physical activity in the independent men and mobility in the institutionalized men were estimated by standard instruments. LBM and bone status at nine skeletal sites were determined by dual X-ray absorptiometry. RESULTS: The BMD and TBBMC values of the free living men were 4-20% higher than those of the institutionalized men. In the independent old men, serum testosterone was the strongest predictor of BMD and TBBMC, while age was the only predictor of LBM. In the chronically institutionalized men, age, body weight and immobility were the strongest predictors of body composition, and testosterone was correlated only with femoral neck BMD. CONCLUSIONS: In aging independent men, low levels of testosterone are associated with demineralization of the skeleton. Immobility and under-weight are associated with the osteopenia of old men residing in nursing homes. In this cross-sectional study of elderly men, there was no evidence of a relation of the somatotrophic axis to bone status or LBM, or of the gonadotrophic axis to LBM.

Activities of Daily Living↗
PubMed1994

Positive and negative symptoms of schizophrenia: past, present, and future.

The "group of schizophrenias," normally referred to with a single nominative, is phenomenologically heterogeneous. Its symptoms represent multiple psychological domains, including perception, inferential thinking, language, attention, social interaction, emotion expression, and volition. Studies of psychopathology have simplified this complex array in several ways; one has been a subdivision into positive and negative symptoms. Reports by our group and others suggest that the symptoms of schizophrenia fall into three natural dimensions: positive symptoms subdivided into psychotic and disorganized dimensions, while a third negative dimension also emerges. Since these dimensions have impressive consistency across studies, future work must examine their relationship to clinically relevant concepts such as prognosis or etiology and examine four different aspects: longitudinal course, neural mechanisms, relationship to treatment, and interrelationships in other pathological conditions.

Brain↗
PubMed1994

Diaspirin crosslinked hemoglobin (DCLHb): control of pressor effect with anti-hypertensive agents.

Diaspirin crosslinked hemoglobin (DCLHb) administration elevates mean arterial pressure (MAP). The purpose of this study was to determine whether commonly used antihypertensive agents could control this pressor effect in rats. Awake rats were injected intravenously (i.v.) with 280 mg/kg of DCLHb. Fifteen minutes later when MAP was 25-30% above baseline and heart rate (HR) was reciprocally decreased, prazosin (2 mg/kg;an alpha adrenergic blocker), nitroglycerine (NTG; 10-150 mcg/min; a nitrovasodilator), nicardipine (0.204-0.08 mg/hr; a calcium channel blocker) or labetalol (5 mg/kg; an alpha/beta adrenergic blocker) was administered i.v. All four classes of antihypertensive agents promptly restored MAP to baseline. Coincident with the return of MAP to baseline, HR was restored to baseline in prazosin and NTG treated animals, however, bradycardia persisted in those animals treated with nicardipine and labetalol, most likely due to the negative chronotropic properties of these agents. We conclude that the pressor effect of DCLHb can be readily controlled with at least four different classes of commonly used antihypertensive agents.

Animals↗