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S Smith

Publications and source records attributed to S Smith.

At least 469 records · Page 26Linked to original sources

Crystallization and preliminary diffraction studies of thioesterase II from rat mammary gland.

Thioesterase II from rat mammary gland has been crystallized in the presence of decanoic acid by the vapor diffusion method. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), and have cell dimensions, a = 52.7 A, b = 78.0 A, and c = 133.6 A. The asymmetric unit likely consists of two protein monomers based on predictions from its calculated Matthews coefficient. Crystals typically diffract to at least 2.5 A resolution and are suitable for X-ray crystallographic analysis.

Animals↗

A property level analysis of lexical semantic representation in Alzheimer's disease.

In order to assess the hypotheses that Alzheimer's disease (AD) results in a property level restructuring, loss, or degradation of lexical-semantic knowledge, Alzheimer's patients and normal elderly subjects were presented with a property verification task in which they were asked to judge the truth value of telegraphic statements which paired objects with their properties (e.g., "Apple is red."). Objects with either high- or low-typical exemplars of categories (e.g., "oak" is a high typical exemplar of the category "tree." while "palm" is a less typical item). Properties were varied with respect to normatively determined dominance (e.g, "fins" is a high dominant property of "trout," while "slimy" is a less dominant property) and whether they were distinctive (i.e., served to distinguish between subsets of exemplars within a category) or shared among most or all category members (e.g., "stem" for the category "fruit"). Analyses of accuracy and reaction time data suggested that AD results in neither a loss per se of representation of properties, nor a reorganization of relations between objects' properties. However, results were consistent with a property level degradation of AD patients' object concepts. While there was no evidence for a differential degradation of distinctive vs shared properties, results suggested that AD patients have degraded representations of lower dominant properties and properties of low-typical category exemplars.

Aged↗

Correlation between toxicity and effects on intermediary metabolism in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male C57BL/6J and DBA/2J mice.

Male mice were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by gavage. C57BL/6J (C57) mice received 0.03 to 235 micrograms/kg, DBA/2J (DBA) mice 1 to 3295 micrograms/kg. On Day 8 after dosing blood was collected, and livers and kidneys were removed. Body weights and feed intake were not much affected until Day 8 after exposure. Hepatomegaly developed at doses above 3 and 97.5 micrograms/kg in C57 and DBA mice, respectively. Ethoxyresorufin O-deethylase activity was induced in liver with an ED50 of 1.1 and 16 micrograms/kg and in kidney with an ED50 of 65 and 380 micrograms/kg in C57 and DBA mice, respectively. The activity of phosphoenolpyruvate carboxykinase (PEPCK) in livers of both mouse strains was reduced over the entire dose range, displaying a plateau in the dose response at the onset of acute toxicity of TCDD. This enzyme activity was decreased by as much as 80% at the respective lethal doses. PEPCK activity in kidney was not affected. Glucose-6-phosphatase activity (G-6-Pase) in liver was altered only in the lethal dose range with a maximum reduction of about 50%. Serum glucose concentration was reduced over the entire dose range, but the reduction was significant only at doses in which G-6-Pase activity was affected, reaching levels as low as 3 mmol/liter in DBA mice. Tryptophan 2,3-dioxygenase activity was not lowered at any dose of TCDD in either mouse strain, and no increase in serum tryptophan levels was observed. Serum levels of thyroxine (T4) and triiodothyronine (T3) were dose dependently decreased over most of the dose range administered, with T3 levels exactly paralleling T4 levels in both mouse strains. It is concluded that TCDD causes acute toxicity in male C57 and DBA mice by a severe reduction of gluconeogenesis, but, in contrast to rats, it does not affect tryptophan homeostasis. Following administration of TCDD serum T3 levels in the mouse appear to correlate with T4 levels, whereas in the rat they are independent of each other.

Animals↗

Evaluation of four animal models of intrarenal calcium deposition and assessment of the influence of dietary supplementation with essential fatty acids on calcification.

Firstly, to determine a satisfactory animal model for induction of intrarenal calcification, a study of four previously described animal models of intrarenal calcification was carried out which showed that intraperitoneal injection of 10% calcium gluconate into female Sprague-Dawley rats was most effective. We then investigated the hypothesis that dietary supplementation with essential fatty acids could reduce the intrarenal calcification developing as a result of intraperitoneal calcium injection. Using a combination of fish oil and evening primrose oil, we demonstrated a significant difference in renal parenchymal calcification, which was 940 +/- 240 micrograms Ca/g dry weight renal parenchyma in unsupplemented animals and 320-370 +/- 55-65 micrograms Ca/g dry weight renal parenchyma in supplemented animals (means +/- SEM, P < 0.005). It was also demonstrated that there was synergism between eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA): dietary supplementation with a combined oil preparation containing 27 mg/ml EPA and 67 mg/ml GLA mixed as 2% with food was as effective as oils containing either 400 mg/ml EPA or 80 mg/ml GLA mixed as 4% of food.

Animals↗

Electroconvulsive shock increases dopamine D1 and D2 receptor mRNA in the nucleus accumbens of the rat.

The present study examined the effects of acute and repeated administration of electroconvulsive shock (ECS) on levels of D1 and D2 receptor mRNAs in the nucleus accumbens and striatum (caudate-putamen) of the rat. Quantitative in situ hybridisation with 35S-labelled oligonucleotide probes specific for D1 and D2 receptor mRNAs was utilised. Compared to controls, rats receiving a single ECS showed higher levels of both D1 and D2 receptor mRNAs in the nucleus accumbens 4 h, but not 24 h, after treatment. Similarly, rats receiving ECS repeatedly (five ECS in 10 days) also exhibited higher levels of D1 and D2 receptor mRNAs in the nucleus accumbens 4 h, but not 24 h, after the last treatment. The effects of single and repeated ECS treatment on dopamine receptor mRNA levels were localised to the caudal region of the nucleus accumbens. No statistically significant changes in mRNA levels were detected in the striatum of rats treated with either acute or repeated ECS. We discuss the possibility that increased expression of D1 and D2 receptors in the nucleus accumbens may be involved in the dopamine-enhancing properties of ECS detected in behavioural studies.

Animals↗

The effect of testing time on students' performance for the subject examination for internal medicine.

The authors tested the hypothesis that increasing the allotted testing time from two to four hours for the National Board of Medical Examiners medicine subject examination would increase the score on this examination when given as part of the clerkship evaluation. One-hundred six students who completed their medicine clerkships between September 1991 and August 1992 (group 1) were compared with 96 students who completed their clerkships between September 1992 and August 1993 (group 2). The mean medicine subject examination score for group 1 was 462 +/- 86, vs 518 +/- 108 for group 2 (p = 0.0003). Regression analysis using the medicine subject examination score as the dependent variable and all baseline characteristics, group assignment, and time of year the test was taken as independent variables demonstrated significant interactions only for United States Medical Licensing Examination (USMLE) Step 1 score (R2 = 0.48, beta weight = 0.68, p = 0.0000) and group assignment (R2 = 0.05, beta weight = 0.18, p = 0.002). The authors conclude that increased testing time for the medicine subject examination from two to four hours is associated with a significant increase in scores; however, scores on the preclinical USMLE Step 1 showed a stronger association.

Adult↗

Evaluation of the medical diagnostic imaging support system based on 2 years of clinical experience.

The Medical Diagnostic Imaging Support (MDIS) system at Madigan Army Medical Center (MAMC) has been operational in a phased approach since March 1992. Since then, nearly all image acquisition has been digital with progressively increasing primary softcopy diagnosis used. More than 375,000 computed radiography (CR) images as well as other modality images have been archived. Considerable experience in installation and implementation phasing has been gained. The location and ergonomic aspects of equipment placement were refined with time. The original clinical scenario was insufficiently detailed and additions were made to facilitate smoother and more complete transition toward a filmless environment. The MDIS system effectiveness and performance have been good in terms of operational workload throughout, background operations, and reliability. The important areas regarding reliability are image acquisition, output, display, database operations, storage, and the local area network. Fail-safe strategies have been continually improved to maintain continuous clinical image availability during the times when the MDIS system or components malfunction. Many invaluable lessons have been learned for effective quality assurance in a hospital-wide picture archiving and communication system. These issues include training, operational quality control, practical aspects of CR image quality, and increased timeliness in the generation and distribution of radiographic reports. Clinical acceptability has been a continuous process as each phase has been implemented. Clinical physicians quickly used the workstations soon after the start of MDIS at MAMC. The major advantage for clinicians has been the amount of time saved when retrieving multimodality images for review. On the other hand, the radiologists have been slower in their acceptance of the workstation for routine use.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗

Determinants of hospital survival after cardiac transplantation.

To identify the preoperative factors that influence hospital survival after transplantation we analyzed our consecutive experience of 183 transplantations in 179 patients over a 10-year period. There were 151 male and 29 female transplant recipients ranging in age from 10 days to 70 years (mean, 48 +/- 1 years). Diagnoses included coronary disease in 110 patients, cardiomyopathy in 55 patients, valvular disease in 6 patients, and congenital heart disease in 9 patients. Seventy-seven had undergone a previous cardiac operation, and 30 patients required preoperative mechanical support. Forty patients received hearts from donors who were 40 years old or older (range, 40 to 62 years). Ischemic time was greater than 240 minutes in 32 cases, and pulmonary vascular resistance was greater than 3 Wood units in 40 patients (range, 3.1 to 10.0 Wood units). Cyclosporine induction was used in 52 patients, whereas 128 recipients received polyclonal antibody prophylaxis. There were 25 hospital deaths. Recipient diagnosis, use of mechanical support, donor age, and the immune suppression protocol were related to hospital survival according to univariate analysis. Using multiple logistic regression, only the method of immune suppression induction and the use of mechanical assists were significant independent determinants of survival. In conclusion, we believe that extended ischemic times and donor age do not adversely affect the early success of transplantation, whereas induction with immune globulin may reduce early mortality. Patients requiring mechanical support before transplantation continue to be a challenge.

Adolescent↗

Limited T cell receptor usage by HTLV-I tax-specific, HLA class I restricted cytotoxic T lymphocytes from patients with HTLV-I associated neurological disease.

T cell receptor (TCR) V alpha and V beta chain usage of HTLV-I tax-specific, HLA class I restricted CD8+ cytotoxic T cells (CTL) was determined from lymphocytes obtained from peripheral blood of patients with HTLV-I associated neurological disease. To characterize TCR repertoire, CD8+ lymphocytes from peripheral blood were cloned in limiting dilution, and the resulting wells were screened for HTLV-I-specific precursor CTL activity. RNA was isolated from HLA-A2 restricted HTLV-I tax peptide-specific (tax 11-19; LLFGYPVYV) CD8+ CTL lines and cDNA was analyzed by PCR amplification using V alpha and V beta chain family-specific oligonucleotide primers. The results indicate that CD8+ cytotoxic T cell lines from HLA-A2 HAM/TSP patients express a limited repertoire of T cell receptor chains which may correlate with duration and severity of disease. The restricted use of TCR genes expressed by antigen-specific CTL may play a critical role in the pathogenesis of HAM/TSP and may be of value in developing immunotherapeutic strategies that focus on eliminating these cells or inhibiting their activity.

Amino Acid Sequence↗

Implementation of an NSOM system for fluorescence microscopy.

We describe our progress toward an NSOM system intended for fluorescence imaging of biological samples. This process included integration of shear-force feedback into an existing NSOM system. Topographic images acquired using uncoated tips are presented. We also present our initial effort at simultaneous acquisition of topographic and fluorescence data using an aluminum coated tip.

Equipment Design↗

Management of synchronous renal cell carcinoma and aortic disease.

BACKGROUND: We have noted a significant incidence of renal cell carcinoma (RCC) detected during evaluation for aneurysmal and aortoiliac occlusive disease. The approach to synchronous malignancy and aortic disease (staged versus concurrent resection) is controversial, as is the management of incidental RCC (partial versus radical nephrectomy). PATIENTS AND METHODS: We reviewed our experience with incidental RCC in patients undergoing aortic reconstruction between 1991 and 1994. Ninety-seven patients underwent aortic reconstruction for aneurysmal (72), occlusive (20), or embolic disease (5) during the time frame under review. All were men. Of the 80 preoperative computerized tomographic (CT) scans obtained, 7 (9%) demonstrated renal lesions suspicious for RCC. All lesions were explored and excised by partial or radical nephrectomy before heparinization and completion of the planned aortic procedure. RESULTS: The overall mortality rate was 3%. None of the deaths occurred in patients undergoing combined procedures. Four partial and three radical nephrectomies were performed. Of the 7 renal lesions, 2 were complex cysts and 5 were RCC. Both patients with complex cysts were treated with wedge resection. One patient required surgical drainage of a wound abscess after partial nephrectomy. No significant differences were found between preoperative (1.4 +/- 0.1 mg/dL) and postoperative (1.8 +/- 0.2 mg/dL) creatinine levels following combined procedures. On follow-up CT scans done at 6-month intervals (mean follow-up 24 months), no evidence exists of recurrence, metastasis, or graft infection. CONCLUSIONS: This patient population demonstrated an unexpectedly high prevalence of incidental RCC (5 or 80 CTs, 6%). No increase in mortality was found when RCC and aortic disease were treated at the same operation. While partial nephrectomy was associated with one wound infection in this series, it is an effective treatment for small incidental RCC and may avoid unnecessary nephrectomy in patients with benign disease. Base on the high incidence of RCC in this population, we recommend exploration of all suspicious lesions. Nephrectomy can be performed safely in the same setting as aortic reconstruction. Because underlying renal dysfunction is not uncommon in patients with aneurysmal and aortoiliac occlusive disease, nephron-sparing surgery should be considered.

Aged↗

The effect of monophasic combinations of ethinyl estradiol and norethindrone on gonadotropins, androgens and sex hormone binding globulin: a randomized trial.

The effects of different monophasic combinations of ethinyl estradiol and norethindrone on FSH, LH, sex hormone binding globulin, total testosterone, androstenedione, and dehydroepiandrosterone sulfate levels in non-obese, non-hirsute women were compared. Retrospective analysis of frozen serum from a prospective randomized trial in which women received one of three oral contraceptive pills containing ethinyl estradiol 50 micrograms/norethindrone 1 mg, ethinyl estradiol 35 micrograms/norethindrone 1 mg or ethinyl estradiol 35 g/norethindrone 0.5 mg for nine cycles was conducted. Blood samples were obtained prior to treatment and during the third, sixth and ninth pill cycles. Ethinyl estradiol 50 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 1 mg suppressed FSH, LH, and total testosterone and increased sex hormone binding globulin to a similar degree. Ethinyl estradiol 35 micrograms/norethindrone 0.5 mg resulted in less suppression of FSH, LH, and total testosterone, but greater elevation of sex hormone binding globulin. Dehydroepiandrosterone sulfate was suppressed to a similar degree with ethinyl estradiol 35 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 0.5 mg, but ethinyl estradiol 50 micrograms/norethindrone 1 mg resulted in the least suppression of dehydroepiandrosterone sulfate. Ethinyl estradiol 35 micrograms/norethindrone 1 mg caused greater suppression of androstenedione than did the other two oral contraceptives. Oral contraceptive-induced changes in gonadotropins, androgens, and sex hormone binding globulin can be predicted by considering the relative amounts of estrogen and progestin in the pill. When combined with 1 mg of norethindrone, 50 micrograms of ethinyl estradiol did not result in greater suppression of FSH, LH, or total testosterone or in greater elevation of sex hormone binding globulin than did 35 micrograms of ethinyl estradiol.

Adolescent↗

Use of postseparation sperm parameters to determine the method of choice for sperm preparation for assisted reproductive technology.

OBJECTIVE: To evaluate strict sperm morphology after preparation of semen specimens using three different sperm separation techniques, since strict morphology correlates well with IVF. DESIGN: Semen from 30 men were analyzed before and after sperm separation using mini-Percoll gradient, direct swim-up, and SpermPrep filtration column (ZBL, Inc., Lexington, KY) methods. SETTING: Assisted Reproductive Technology laboratory at Sinai Hospital of Baltimore. MAIN OUTCOME MEASURES: Primary end points measured were percent morphologically normal sperm and percent improvement in sperm morphology, using Kruger strict criteria. Secondary factors determined were percent motility, improvement in motility, hypoosmotic swelling, improvement in hypoosmotic swelling, and 24- and 48-hour sperm survival under simulated IVF conditions. RESULTS: Mini-Percoll produced specimens with significantly greater normal sperm morphology, morphology improvement, motility, hypoosmotic swelling, and survival than obtained with the other two separation methods. For 25 of 30 specimens, mini-Percoll yielded the greatest number of morphologically normal, motile sperm that survived for 24 hours. In four instances, mini-Percoll was associated with an increased percentage of acrosomal abnormalities despite an overall improvement in morphology. Hypoosmotic swelling scores were lower in two subjects after mini-Percoll sperm separation and in three subjects for each of the other methods. CONCLUSIONS: Data suggest that mini-Percoll is superior to swim-up or SpermPrep for producing specimens with enhanced morphology, motility, and in vitro survival. However, no single separation technique is always superior, and methodology may induce damage to the acrosome or sperm membranes. Sperm specimens should be evaluated individually to determine the best separation method before actual ART cycles. The technique that yields the most morphologically normal, motile sperm that survive in culture should be used for ART procedures.

Cell Separation↗

Immunodeficiency in long-term survivors of acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster therapy.

OBJECTIVE: To determine whether the immune systems of long-term survivors of acute lymphoblastic leukemia (ALL) have persistent immune defects after Berlin-Frankfurt-Münster (BFM) treatment. STUDY DESIGN: We evaluated the cellular and humoral immune responses of 13 children with ALL in complete remission and off modified protocol treatment for 2 or more years. All patients had received complete immunizations for measles, mumps, rubella, and poliovirus before ALL developed. They were challenged with Haemophilus influenzae type B (Hib) and Pneumococcus vaccines after baseline serum samples were obtained. We also determined in vivo humoral immune responses to bacteria and viruses that cause common pediatric diseases. RESULTS: Compared with age-matched control subjects, the long-term survivors of ALL had a significant difference in the presence of protective antibodies to measles (p < 0.0001) and polioviruses (p < 0.0001) in their baseline sera; more than half had no protective antibodies to one or more previously administered vaccines or related infections. Most produced protective concentrations of specific antibody after reimmunization, but some were repeatedly unable to make protective antibodies, or mount a normal antibody response, despite natural disease and/or revaccination. Four children had significant infections. CONCLUSIONS: Long-term survivors of ALL who had BFM treatment may have persistent immune defects with respect to common childhood bacterial and viral diseases they previously had, or vaccines they received.

Adolescent↗

Allograft heart valve sterilization: a six-year in-depth analysis of a twenty-five-year experience with low-dose antibiotics.

At the Prince Charles Hospital, from a 25-year experience with allograft heart valves (1969 to 1994), a 6-year analysis from March 1988 to August 1994 of the contamination rates and efficiency of a short-duration, low-dose antibiotic sterilization protocol was made. This analysis covered 642 collections and 680 aortic and pulmonary valve implants. Tissue samples obtained at collection, valve trimming, postantibiotic incubation, and implant provided the raw data. At collection, valves retrieved in open mortuaries produced the highest contamination rate of 54%. Minimal exposure to antibiotics during transport and trimming reduced the contamination rate to 11% (p < 0.05). This was similar to the contamination rate at trimming for valves collected in the "sterile" operating room from multiorgan donors (12%). Antibiotic incubation at 37 degrees C for 6 hours reduced the contamination rate to 4% (p < 0.05). Only valves that showed no contamination at cryopreservation were implanted. However, at implant, resected tissue from valves that had been incubated in antibiotics showed a contamination rate of 3%, presumably from the theater environment, compared with 15% (p < 0.05) for tissue from valves that had not been incubated. A residual antibiotic effect appears present at the time of implant in valves that have been incubated in antibiotics and may assist in the reduction of and resistance to infection in the immediate postoperative period. This is supported by the low incidence of endocarditis in the first 3 postoperative months. The simple and effective protocol of collection within 24 hours of death combined with low-dose antibiotic sterilization is sufficient to produce pathogen-free valves in the majority of cases (> 95%).

Anti-Bacterial Agents↗

Hepatic metabolic response to injury and sepsis.

BACKGROUND: Experimental reports have indicated that hepatic oxidative and synthetic metabolism may become depressed in sepsis. Because the mechanism of infection-related liver dysfunction has not been established, further study of these functional alterations could contribute to the therapeutic management of septic organ failure syndromes. However, recently controversy has arisen over the existence of these derangements that must be reconciled before further progress in this field can be made. METHODS: Splanchnic balance studies for the measurement of glucose output and oxygen consumption were used to assess hepatic function in fasted normal volunteers (n = 18), injured patients (n = 10), and patients with sepsis (n = 18). The liver's contribution to splanchnic metabolism was estimated from a comparison of splanchnic oxygen utilization in response to increases in the liver-specific process of glucogenesis. In addition, in vivo liver albumin production was determined by using the [14C] carbonate technique. RESULTS: Glucose output after injury and sepsis was increased by 12.8% and 76.6%, respectively, compared with controls. On the basis of substrate balance studies, gluconeogenesis was estimated to account for 46%, 87%, and 93%, respectively, of splanchnic glucose output in each of the three groups. In patients with sepsis glucose output was also noted to be linearly related to regional oxygen consumption, indicating that these processes were coupled and increases in the respiratory activity of the splanchnic cellular mass could be accounted for by increases in new glucose output and gluconeogenic substrate clearance. The mean albumin synthetic rate increased during injury and sepsis by 22% and 29%, respectively, compared with normal volunteers. CONCLUSIONS: These studies cast doubt on the commonly held notion that tissue respiratory dysfunction may occur during sepsis. On the contrary, hepatic function is accelerated during hyperdynamic sepsis, and evidence indicating oxidative or synthetic functional depression is lacking.

Adult↗