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D K Smith

Publications and source records attributed to D K Smith.

At least 55 records · Page 3Linked to original sources

Prediction of nocturnal plasma melatonin from morning urinary measures.

A growing literature indicates that blood levels of the hormone melatonin may have important implications for human health and well-being. Melatonin is synthesized and released into the general circulation at night, however, and it is seldom feasible to draw blood samples at night in epidemiological studies. There is some evidence that levels of urinary melatonin and of 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin, accurately reflect nocturnal plasma melatonin. If this is the case, urinary assays could be powerful tools for epidemiological studies. A laboratory-based study was performed to examine the relationships between nocturnal plasma melatonin, morning urinary melatonin, and morning urinary aMT6s levels in 78 men. The relationship between total nocturnal plasma melatonin and both urinary aMT6s corrected for creatinine and urinary melatonin is significant. Combining the two urinary measures accounts for 72% of the variance in total plasma melatonin. Peak nocturnal plasma melatonin also was significantly related to urinary melatonin and to aMT6s. The urinary measures show good sensitivity and specificity in identifying individual differences in nocturnal plasma melatonin levels. These results support the inclusion of morning urine samples to assess the contribution of the hormone melatonin in occupational or residential studies involving healthy, young men.

Adolescent↗

Measurement of exercise dependence in bodybuilders.

OBJECTIVE: The purpose of this study was to explore exercise dependence in bodybuilders, and undertake preliminary validation of a measurement instrument. EXPERIMENTAL DESIGN: A comparative analysis of self-report indices between groups. PARTICIPANTS: Forty-seven bodybuilders, 31 individuals who weight trained for general fitness purposes and 24 weightlifters participated in the study. MEASURES: Each subject completed the following: demographic information, bodybuilding-specific versions of the social identity and exclusivity scales of the Athletic Identity Measurement Scale, the physical strength and body attractiveness subscales of the Physical Self-Perception Profile, a short form of the Marlowe-Crowne Social Desirability Scale, and a 9-item Bodybuilding Dependence Scale. RESULTS: Factor analysis on the BDS revealed 3 subscales (social dependency, training dependency and mastery) which accounted for 68.4% of the variance. Internal consistency was satisfactory for each subscale (Chronbach's alpha = 0.76, 0.75 and 0.78 respectively). The BDS social dependency and PSPP body attractiveness scores of the bodybuilders were higher than those of the weightlifters, whose scores were higher than those of the fitness trainers. The bodybuilders scored higher on both AIMS subscales than the other groups. The bodybuilders and weightlifters scored higher on PSPP physical strength than the fitness trainers. BDS social dependency correlated with both AIMS and both PSPP subscales, and BDS training dependency correlated with AIMS exclusivity. All three BDS subscales correlated with training frequency. Discriminant analysis found the combination of AIMS social identity, BDS social dependency and years training experience enabled correct classification of 92% of the respondents. CONCLUSIONS: These results support the construct and concurrent validity of the BDS social dependency subscale, but do not wholly support the validity of the other two subscales.

Adult↗

Sequence profiles of immunoglobulin and immunoglobulin-like domains.

Immunoglobulins (Ig) are highly modular proteins, consisting of variable and constant domains, which have clear, conserved sequence patterns. These sequence patterns have allowed T-cell receptor (TCR) and major histocompatibility complex (MHC) molecule domains, as well as some cell adhesion, cell surface receptor and muscle protein domains, to be identified as forming a superfamily of related proteins together with the Ig-domains. The domains of these proteins have been grouped into four sets: variable (V-set), constant-1 (C1-set), constant-2 (C2-set) and intermediate (I-set). X-ray and NMR studies have shown that these domains form a Greek-key beta-sandwich structure with the sets differing in the number of strands in the beta-sheets as well as in their sequence patterns. The conserved sequence elements in the major sets of Ig and Ig-like molecules have previously been reported as general sequence profiles. This work examines the variability within these sets. Detailed sequence profiles and consensus sequences for these sets and groups have been constructed and a novel form of presentation has been developed to overcome some of the drawbacks of current methods of presenting consensus sequences. The profiles that were constructed allow a comparison of the similarities and differences among the sets of Ig and Ig-like sequences and provide a means by which sequences can be tested for compatibility with Ig-like sequence motifs. As well, the sequence separations of the main residues in the characteristic "pin" structure of Ig-like molecules were examined for variation among the groups. From the profiles constructed here, measures of the degree of conservation within the groups of molecules were determined. These measures were used to assist in a reconsideration of possible evolutionary pathways between the major structural groups of the Ig-superfamily.

Amino Acid Sequence↗

Identification of a ligand-binding site on the granulocyte colony-stimulating factor receptor by molecular modeling and mutagenesis.

Granulocyte colony-stimulating factor (G-CSF) initiates its effects on cells of the neutrophil lineage by inducing formation of a homodimeric receptor complex. The structure of the G-CSF receptor has not yet been determined, therefore we used molecular modeling to identify regions of the receptor that were likely to be involved in ligand binding. The G-CSF receptor sequence was aligned with all the available sequences of the gp130 and growth hormone receptor families and a model of the cytokine receptor homologous domain was constructed, based on the growth hormone receptor structure. Alanine substitution mutagenesis was performed on loops and individual residues that were predicted to bind ligand. Mutant receptors were expressed in factor-dependent Ba/F3 cells and assessed for proliferation response and ligand binding. Six residues were identified that significantly reduced receptor function, with Arg288 in the F'-G' loop having the greatest effect. These residues formed a binding face on the receptor model resembling the growth hormone receptor site, which suggests that the model is reasonable. However, electrostatic analysis of the model provided further evidence that the mechanism of receptor dimerization is different from that of the growth hormone receptor.

Amino Acid Sequence↗

Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice.

BACKGROUND: We performed ex vivo adenoviral gene transfer in a mouse pancreatic islet transplant model to test the efficacy of this expression system. We then determined whether adenoviral-mediated expression of mouse interleukin (IL) 4 or IL-10 from transduced syngeneic islet grafts could prevent disease recurrence in diabetic nonobese diabetic (NOD) mice. METHODS: An adenoviral vector expressing beta-galactosidase (AdCMV betaGal) was used to transduce BALB/c islets (2.5 x 10(3) plaque-forming units/islet), which were analyzed for glucose responsiveness, islet cell recovery, and efficiency of gene transfer. In vivo function and reporter gene expression were examined with AdCMV betaGal-transduced islet grafts in alloxan-induced diabetic syngeneic recipients. Adenoviruses expressing either IL-4 or IL-10 were used in a similar fashion to infect NOD islets, which were characterized in vitro, as well as transplanted into diabetic syngeneic recipients. RESULTS: In vitro functional studies showed no significant difference between control or transduced islets, with 50+/-4% of AdCMV betaGal-infected islet cells staining positive for beta-galactosidase. Transplant recipients became nomoglycemic within 48 hr after transplant, and, although beta-galactosidase expression decreased over time, it was detectable in the graft for up to 8 weeks. Despite the nanogram quantities of IL-4 or IL-10 produced/day from each graft equivalent in vitro, transduced and transplanted NOD islets failed to prevent disease recurrence. CONCLUSIONS: These results suggest that adenoviruses are efficient for at least medium term gene expression from islets in vivo, but neither IL-4 nor IL-10 alone can prevent autoimmune disease recurrence in NOD mice.

Adenoviridae↗

Design and baseline participant characteristics of the Human Immunodeficiency Virus Epidemiology Research (HER) Study: a prospective cohort study of human immunodeficiency virus infection in US women.

The prospective, multisite human immunodeficiency (HIV) Epidemiology Research Study was established to define the biologic, psychologic, and social effects of HIV infection on the health of US women. From 1993 to 1995, a total of 871 HIV-infected women and 439 demographically matched, uninfected women aged 16-55 years, half of whom reported injection drug use and half of whom reported only sexual risk behaviors, were recruited in four US cities. Two sites recruited primarily from medical/drug therapy care settings, and two recruited from community sources. Women consented to biannual interviews; physical examination; blood, urine, and cervicovaginal specimen collection and repository; laboratory assays; and abstraction of outpatient and inpatient medical records to document HIV and acquired immunodeficiency syndrome-related diagnoses. Retention was greater than 88% at the third 6-month follow-up. Lower retention was associated with currently injecting drugs, not having dependent children, and not being infected with HIV at enrollment. In addition to the core study, a variety of nested studies are under way, some in collaboration with other HIV cohorts and various Public Health Service agencies. This cohort is distinct from other HIV longitudinal cohorts in the diversity of its participants and the comprehensive range of measures to study prospectively the biomedical, social, and emotional effects of the HIV epidemic on infected women and those whose behavior puts them at high risk of infection.

Adolescent↗

Interleukin-6: structure-function relationships.

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

Amino Acid Sequence↗

MR imaging of musculoskeletal tumors and tumor mimickers with intravenous gadolinium: experience with 242 patients.

PURPOSE: This pictorial essay reviews our experience with MR scans with gadolinium in patients with musculoskeletal tumors and tumor mimickers. DESIGN: Review of 242 MR scans obtained in the initial evaluation of a possible primary musculoskeletal neoplasm. All scans included a T1-weighted, fat-suppressed sequence following intravenous administration of gadolinium. RESULTS: MR scans with gadolinium did not contribute to differential diagnosis or patient management in 89% of the patients in this series. However, intravenous gadolinium did assist in guiding the biopsy of bulky lesions and evaluating treated tumor beds for possible recurrence. MR scans with gadolinium were sometimes helpful when the differential diagnosis included synovitis, Morton's neuroma or intramuscular myxoma, and when it was important to differentiate cystic from solid lesions. CONCLUSIONS: Routine use of gadolinium in every initial MR examination of a possible musculoskeletal mass is not warranted. However, there are appropriate selected indications for gadolinium administration as outlined above.

Adolescent↗

Large scale isolation, growth, and function of porcine neonatal islet cells.

Based upon existing methods of isolating fetal porcine islet tissue, a simple, reliable procedure was developed for the preparation of porcine neonatal islet cell aggregates with a reproducible and defined cellular composition. After 9 d of in vitro culture, tissue from one neonatal pig pancreas yielded approximately 50,000 islet cell aggregates, consisting of primarily epithelial cells (57%) and pancreatic endocrine cells (35%). During the culture period, the total beta cell mass decreased initially, but subsequently increased 1.5-fold between days 3 and 9. Transplantation of grafts consisting of 3 x 10(5) beta cells (1,000 aggregated) under the kidney capsule of alloxan-diabetic nude mice corrected hyperglycemia in 75% (10/13) of the animals, whereas, 100% (20/20) of recipients implanted with 6 x 10(5) beta cells (2,000 aggregates) achieved euglycemia within 8 wk posttransplantation. Nephrectomy of the graft bearing kidney at 14 wk posttransplantation resulted in hyperglycemia in all recipients, and examination of the grafts revealed the presence of numerous well-granulated insulin- and glucagon-containing cells. The cellular insulin content of these grafts was 20 to 30-fold higher than at the time of transplantation. These results indicate that the neonatal porcine pancrease can be used as a source of large numbers of viable islet cells, which have the potential for growth both in vitro and in vivo, and exhibit the metabolic capacity to correct diabetes in nude mice.

Animals↗

Magnetic resonance imaging characteristics of a lead pencil foreign body in the hand.

Foreign body detection and removal from the hand can present a challenging problem for the hand surgeon. Imaging studies often are of little help and may even be misleading regarding the size and location of the object. This article reports imaging techniques used in the detection of foreign bodies and presents a case in which magnetic resonance imaging was used to localize a lead-pencil foreign body in the hand prior to surgical removal. We also present the results of magnetic resonance imaging analysis of several lead pencils, showing a similar signal that indicates that iron and magnesium were responsible for the artifact seen on the magnetic resonance image.

Adult↗

Coccidioidomycosis in patients infected with human immunodeficiency virus: review of 91 cases at a single institution.

We retrospectively evaluated the clinical manifestations, diagnosis, treatment, and outcome of coccidioidomycosis in 91 patients infected with human immunodeficiency virus (HIV) at a single institution. Coccidioidomycosis was the AIDS-defining illness in 37 patients. Fever and chills, weight loss, and night sweats were the most frequent symptoms. The lung was the most frequently involved organ (80%), followed by the meninges (15%). A diffuse reticulonodular infiltrate was seen in 59 patients (65%), and 13 (14%) had focal pulmonary disease; for 15 patients (16%), the chest radiograph was normal. Coccidioidal serologies were positive for 60 patients (68%), while for 23% with proven coccidioidomycosis such tests were negative Most patients were treated with systemic amphotericin B and then an oral azole. The mortality for the whole group was 60%. Patients with diffuse pulmonary disease had the highest mortality (68%), with a median duration of survival of 54 days (P < .05; 95% confidence interval, 147-175 days). The presence of diffuse pulmonary disease and a CD4 lymphocyte count of < 50/microL were independent predictors of death. In our experience, coccidioidomycosis is an important opportunistic infection that causes substantial morbidity and mortality among HIV-infected patients living in an area of endemicity.

AIDS-Related Opportunistic Infections↗

Anatomic significance of magnetic resonance imaging findings in hip fracture.

This study was done to determine the histologic etiology for the linear black signal seen on magnetic resonance imaging at the site of proximal femoral fractures. No previous satisfactory explanation for this black line exists in the literature. To determine the pathologic etiology of this linear black signal, the magnetic resonance imaging appearances of osteotomies and fractures of proximal femora were correlated with gross and histologic appearances in 12 freshly frozen porcine hips. In phase 1, a unilateral femoral neck osteotomy was performed in 1 hip, and a sham operation was performed on the contralateral hip. The radiologist was able to easily determine the site and side of the osteotomy using magnetic resonance imaging. In phase 2, the remaining 8 femoral specimens were stressed using the 1125 Instron Materials Testing Machine in a compression mode. In the 8 specimens, 4 fractures were created that were visible on magnetic resonance imaging and plain radiographs; 2 fractures were apparent only on magnetic resonance images, and 2 specimens did not have fractures identified by plain radiographs or magnetic resonance images. Gross and microscopic analysis of the specimens confirmed the magnetic resonance imaging findings in all 8 cases (6 fractures and 2 nonfractures). Histologic evaluation showed trabecular impaction at the 6 fracture sites corresponding to the linear black signal on magnetic resonance images. No edema or hemorrhage was present in these postmortem specimens. The authors conclude that the low signal band seen with proximal femoral fractures is produced by impaction of the trabecular bone and is not the result of perifracture edema or hemorrhage.

Animals↗

Sublabral recess of the superior glenoid labrum: study of cadavers with conventional nonenhanced MR imaging, MR arthrography, anatomic dissection, and limited histologic examination.

PURPOSE: To evaluate size, location, and appearance of the sublabral recess of the superior glenoid labrum, which mimics a superior labral tear oriented in the anterior to posterior direction (SLAP) lesion with conventional magnetic resonance (MR) imaging, MR arthrography, gross dissection, and limited histologic evaluation. MATERIALS AND METHODS: Twenty-six cadaveric shoulder specimens that were freshly frozen were examined with nonenhanced MR imaging and with MR arthrography after intraarticular injection of dilute contrast material with gadolinium. In all specimens, the appearance of the superior glenolabral junction was categorized and was correlated to that seen at gross anatomic dissection. Histologic sections were obtained of two shoulders with large sublabral recesses in the plane of the MR sections. RESULTS: A sublabral recess was present in 19 (73%) shoulders and was deeper than 2 mm in 10 (39%). MR arthrography better demonstrated the sublabral recess than nonenhanced MR imaging. In 16 of 19 shoulders, the sublabral recess was located in the most anterior section obtained through the superior labrum. There was no definite correlation between subject age and sex and glenolabral junction type. At histologic examination of the two shoulders, a synovial lining of the sublabral recess was seen and there was no evidence of fibrosis to suggest a traumatic cause. CONCLUSION: A sublabral recess is common in cadaveric shoulders and has an appearance similar to that of published examples of SLAP lesions. Histologic findings were consistent with normal anatomic structure rather than with acquired, posttraumatic lesions.

Cadaver↗

MR imaging of the anterior cruciate ligament: frequency of discordant findings on sagittal-oblique images and correlation with arthroscopic findings.

OBJECTIVE: The purposes of this study were to determine the frequency of discordant MR findings of the anterior cruciate ligament (ACL) using sagittal-oblique images and the arthroscopic integrity of the ACL in knees with a discordant MR appearance. MATERIALS AND METHODS: The frequency of discordant MR features was determined by independently reviewing the sagittal-oblique images of 53 consecutive patients undergoing subsequent arthroscopic surgery. The first 25 consecutive knees were examined using a conventional, dual-echo, T2-weighted spin-echo (SE) sequence; the subsequent 28 consecutive knees were examined using both a T1-weighted SE(T1) and a fat-suppressed, fast spin-echo (FSE) T2-weighted sequence. Two examiners who were unaware of patient identification and arthroscopic results evaluated only the sagittal images that included the ACL. Each reviewer graded the ACL as torn or intact. The MR appearance was considered discordant when one MR sequence showed disrupted or poorly seen ACL fibers and the other sequence showed intact ACL fibers. The arthroscopic integrity of the ACL was determined for the 20 knees with a discordant MR appearance. RESULTS: A discordant MR appearance of the ACL was seen in 20 of the 53 knees (38%), including 10 knees evaluated using conventional T2-weighted sequences (40%) and 10 knees using T1/FSE T2 (36%) sequences. Arthroscopic examination of these knees showed intact ACL fibers in all 20 knees; the ACL was normal in 18 knees and a partial tear was questioned in two knees. CONCLUSION: A discordant appearance of the ACL was frequently encountered (38%) using either conventional T2-weighted sequences or T1 and FSE MR sequences in the sagittal-oblique plane. Intact ACL fibers were found during arthroscopy in all 20 knees with a discordant MR appearance.

Adult↗

Avulsion fractures of the volar aspect of triquetral bone of the wrist: a subtle sign of carpal ligament injury.

OBJECTIVE: We report five examples of a triquetral fracture pattern not previously described to our knowledge. These fractures from the volar aspect of the triquetral bone are important because they are easily missed with conventional wrist radiographs and yet are associated with significant ligament injuries and carpal instability. MATERIALS AND METHODS: Five volar triquetral avulsion fractures occurred in young men (20-28 years old) during falls while playing sports. The initial evaluation consisted of a three-view radiographic series. Subsequently, an instability series was obtained in each case. Four patients were also evaluated by stress videofluoroscopy and arthrography, one by CT, and four by MR imaging. RESULTS: None of the five fractures was recognized on radiographs obtained in the emergency room. Each fracture was identified on an instability series and involved the radial aspect of the volar surface of the triquetral bone. All four wrists evaluated by stress videofluoroscopy showed lunatotriquetral joint instability. One also showed instability of the scapholunate joint. All four wrists evaluated by arthrography showed tears of the lunatotriquetral ligament and three had an associated tear of the scapholunate ligament. MR examination of four wrists showed a volar capsular ligament attached to the avulsion fracture fragment in each wrist. Two of the patients were treated by arthroscopic debridement and three were treated by prolonged splinting. All five patients had persistent pain and carpal instability of variable severity at least 1 year after injury. CONCLUSION: This avulsion fracture of the radial aspect of the volar triquetral bone is a subtle, easily missed sign of a significant injury of the perilunate ligaments. When this fracture is identified, we recommend further evaluation for associated ligament injury and carpal instability.

Adult↗

MR imaging of occult traumatic fractures and muscular injuries of the hip and pelvis in elderly patients.

Recent studies have shown the usefulness of T1-weighted MR imaging for identifying fractures of the proximal femur in elderly patients with negative radiographs after acute trauma [1-4]. The advent of fast spin-echo and fast inversion recovery sequences allows for the rapid identification of a variety of other musculoskeletal injuries of the hip and pelvis that may explain a patient's symptoms but that may not be seen on T1-weighted images. This pictorial essay shows the types of lesions encountered. Lesion prevalence is given for 20 consecutive patients examined.

Acetabulum↗