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Biomedical subjects

S D Smith

Publications and source records attributed to S D Smith.

At least 109 records · Page 6Linked to original sources

Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos.

Nucleus transfer for the production of multiple embryos derived from a donor embryo relies upon the reprogramming of the donor nucleus so that it behaves similar to a zygotic nucleus. One indication of nucleus reprogramming is the RNA synthetic activity. In normal bovine embryogenesis, the embryo relies upon maternally derived RNA transcripts up to the 8-cell stage, at which time it begins to transcribe its own RNA. In this experiment, RNA synthesis was detected in nucleus transfer embryos (NTE) and control embryos by pulsing with 3H-uridine, fixation, and autoradiography on semithin sections. NTE were produced using either a MII phase (nonactivated) cytoplasts at 32 hr of maturation or S-phase (activated) cytoplasts activated with calcium ionophore A23187 and cycloheximide treatment approximately 8 hr prior to fusion with a blastomere from an in-vitro-produced morula stage embryo at 32 hr of maturation. Control in-vitro-produced embryos were 3H-uridine-labelled and fixed at the 2-, 4-, early 8-, and late 8-cell stages. NTE were similarly prepared at 1, 3, and 20 hr postfusion and at the 2-, 4-, and 8-cell stages. In the control embryos, RNA synthesis was absent in the 2-, 4-, and early 8-cell stages, whereas in all late 8-cell stages, it was present. In NTE from nonactivated (MII phase) cytoplasts, there was a sharp decline in RNA synthesis at 1 hr and 3 hr after fusion and a total absence by 20 hr after fusion. In contrast, NTE from activated (S phase) cytoplasts exhibited continued high levels of RNA synthesis at 1 hr and moderate levels at 3 hr after fusion, although it had ceased by 20 hr after fusion. In all NTE (activated and nonactivated cytoplasts), there was no RNA synthesis seen at the 2-cell stage. However, at the 4-cell stage, weak RNA synthesis was seen in all NTE from activated cytoplasts, whereas none was observed in those from MII nonactivated cytoplasts. At the 8-cell stage, nearly all NTE from S-phase cytoplasts showed weak to moderate levels of RNA synthesis. We conclude that the nucleus reprogramming differs between NTE reconstructed from activated and nonactivated cytoplast with the former undergoing a slower cessation of RNA synthesis after fusion and earlier resumption of RNA synthesis, occurring as early as the 4-cell stage.

Animals↗

State of dermatology training: the residents' perspective.

Changes in health care delivery necessitate modification in dermatology training. While the residents at The University of Alabama at Birmingham were planning their 1995-1996 curriculum, several questions regarding the most appropriate allocation of time and resources arose. Interest in other residency curricula prompted the development of a national survey of dermatology residents. Our purpose was to provide comprehensive data regarding the didactic, clinical, surgical, and other aspects of today's U.S. dermatology residency training from the perspective of the residents. It is hoped these data will assist dermatology residency programs with evaluation of their current curricula. A comprehensive 31-question multiplechoice survey was mailed to 631 residents in 70 U.S. dermatology residency programs. Results were tabulated and median values and percentages of responses were obtained. A Wilcoxon rank-sum test, a chi-square analysis, and logistic regression analysis were performed on survey items on the basis of residents' satisfaction with the training program. Two hundred forty-eight responses (39%) were returned with all years of training well represented. Median values and percentages obtained outlined the didactic, clinical, surgical, and other aspects of dermatology residency training. Seventeen percent of residents believed they were not being adequately trained. Satisfaction with training was noted with more didactic faculty involvement, consultations and research, and surgical procedures performed per month. Residents with enriched didactic, clinical, and surgical training experiences are more satisfied with their training programs.

Alabama↗

Nitric oxide synthase induction with renal transplant rejection or infection.

Nitric oxide (NO) is readily oxidized to nitrate and nitrite and NO activates guanylyl cyclase, increasing cyclic GMP levels. To determine if nitric oxide synthase (NOS) is present in urine collected daily from patients following renal transplantation, we evaluated NOS activity in the leukocyte-rich particulate fraction and measured nitrate, nitrite, and cyclic GMP levels in the supernatant fraction of the urine. Reverse transcriptase-PCR and cDNA sequencing confirmed the presence of inducible NOS (iNOS) in cells obtained from the urine of renal transplant patients with rejection. NOS activity was elevated significantly in renal transplant patients with rejection (6.40 +/- 1.47 pmol citrulline/min/mg protein) or with urinary tract infection (29.56 +/- 11.00 pmol citrulline/min/mg protein), when compared to post-renal transplantation patients without rejection or urinary tract infection (0.51 +/- 0.21 pmol citrulline/min/mg protein). Nitrate levels increased in renal transplant patients with rejection and nitrite levels increased in renal transplant patients with urinary tract infection (UTI). Cyclic GMP levels increased with both rejection and UTI. This study demonstrates the presence of NOS activity and inducible NOS-mRNA in cells isolated from the urine of patients undergoing renal allograft rejection.

Adult↗

A three-dimensional airway assessment for the treatment of snoring and/or sleep apnea with jaw repositioning intraoral appliances: a case study.

The purpose of this snoring/sleep apnea study was to assess the role of 3-D magnetic resonance imaging (MRI) of the airway correlated to jaw reposturing/intraoral appliance design. A clinical case is presented utilizing this technology, integrating a diagnostic baseline and follow-up sleep study/ polysomnograph. The baseline polysomnography, prior to jaw repositioning appliance design, indicated a respiratory disturbance index (RDI) of 21.5 hypopnea/apneas per hour. The follow-up sleep study, with use of an intraoral repositioning appliance, showed a 3.9 per hour RDI, an 82% RDI reduction/improvement. Magnetic resonance TMJ and airway images were done. The MRI enhanced airway assessment computer software program analyzed the 3-dimensional volume and cross sectional area changes from hard/soft palate junction to epiglottis. Imaged were the oropharynx nasopharynx and hypopharynx regional anatomy. The baseline, without mandibular positioning device, showed a total airway volume of 5,801.31 cubic mm, whereas with the mandibular positioning device in place, the total airway volume was increased to 8,657.22 cubic mm or a total increased volume of 32%. The largest improvement site in the airway was the mid-soft palatal uvula/nasopharynx region, with base of tongue moving forward. Along with traditional polysomnography, 3-dimensional MRI airway imaging should be considered as a diagnostic procedure in assessing sleep apnea patients. The necessity of a combined medical/dental team approach is emphasized.

Adult↗

Is computed tomography a useful adjunct to the clinical examination for the diagnosis of pediatric gastrointestinal perforation from blunt abdominal trauma in children?

Perforations of the gastrointestinal (GI) tract, compared to solid organ injuries, are a relatively infrequent sequela of blunt abdominal trauma in children. The purpose of this study is to review retrospectively the diagnostic modalities used in 30 children with proven traumatic intestinal perforations treated at one institution. Since computed tomography with intravenous and oral GI contrast is commonly used in the diagnosis of suspected solid organ injury from blunt abdominal trauma, we evaluated retrospectively the computed tomographic (CT) scan findings in these children in an attempt to accurately predict or suggest GI perforation. Between January 1987 and December 1993, 5,795 children were admitted. Three hundred fifty suffered blunt abdominal trauma of which 30 patients (8.5%) required surgery for a GI perforation and formed the basis for this study. Data collected were mechanisms of injury, results of admission and serial clinical examinations, results of radiologic imaging, associated injuries, operative findings, and outcome. Follow-up was obtained on all patients and averaged 2.5 years. Blows to the abdomen (handlebars, cars, kicks) were the most common cause of perforation, followed by seatbelt injuries. Eleven patients underwent immediate laparotomy an average of 0.75 hours after admission. The indication for surgery was shock (three), clinically apparent peritonitis (five), and free air on plain abdominal radiograph (three). Nineteen patients underwent "later" laparotomy, an average of 3.4 hours after admission, all because of the eventual development of peritonitis. Retrospective review of these CT scans revealed free air anterior to the liver in three, and the remaining 16 had CT findings suggestive of GI injury such as free fluid, focal fluid-filled thick-walled bowel loops, and mesenteric infiltration. There were five (26%) false negative CT scans performed an average of 5.0 hours after injury. We believe serial physical examinations are the gold standard for diagnosing pediatric GI perforation from blunt abdominal trauma. The CT scan may be a useful adjunct to the diagnosis of an intestinal perforation in patients who have no immediate indication for surgery. Presently, the only CT finding that is an absolute indication for laparotomy is free air (in the absence of pulmonary/mediastinal injury or barotrauma). The other CT "findings" need to be validated prospectively.

Abdominal Injuries↗

Deletion or lack of expression of CDKN2 (CDK4I/MTS1/INK4A) and MTS2 (INK4B) in acute lymphoblastic leukemia cell lines reflects the phenotype of the uncultured primary leukemia cells.

The CDKN2 gene has been recently localized to a chromosomal region found to be deleted in leukemias and solid tumors. CDKN2 encodes a 16 kDa protein product (p16INK4A), which functions as a specific inhibitor or the cyclin-dependent kinases 4 and 6. There have been many reports indicating a higher frequency of deletions of the CDKN2 gene in a variety of tumor cell lines, in comparison to primary tumors. These studies raise the possibility that deletions of CDKN2 may be a rare event in primary tumors, and in fact arise in vitro, during the establishment of permanent cell lines. To address this issue, we determined whether the CDKN2 gene deletions found in acute lymphoblastic leukemia (ALL) cell lines are also detected in the primary leukemia samples. Eleven cell lines were identified which had available frozen primary samples of their original leukemic tissue. Five out of 11 of these cell lines, as well as their primary samples had homozygous CDKN2 deletions. The remaining six cell lines and their primary samples retained at least one copy of the CDKN2 gene. Of the six CDKN2+ cell lines, five expressed CDKN2 mRNA, but only one of these expressed the p16 protein product (as did its primary sample). Our results indicate that CDKN2 deletions present in the studied ALL cell lines arose in the primary leukemic cells, and not during cell line establishment or prolonged in vitro culture.

Blotting, Southern↗

Urinary nitric oxide synthase activity and cyclic GMP levels are decreased with interstitial cystitis and increased with urinary tract infections.

PURPOSE: Since urinary nitric oxide synthase (NOS) activity correlates with certain disease process affecting the urinary tract and since nitric oxide increases cyclic GMP levels by activating guanylyl cyclase, urinary particulate NOS activity and cyclic GMP levels are evaluated in female patients with interstitial cystitis (IC) and compared with those from female controls and female patients with urinary tract infections (UTIs). MATERIALS AND METHODS: Urinary NOS activity is measured as the formation of [(14)C]-L-citrulline from [(14)C]-L-arginine, and urinary cyclic GMP levels are measured by an [(125)I]-radioimmunoassay. RESULTS: Female patients with IC have significantly less NOS activity in their urine pellet particulate fractions than female control females UTIs, 2.3 +/- 1.0, 14 +/- 3.0, and 120 +/- 10 pmol. citrulline formed/min./mg. protein. Urinary cyclic GMP levels are significantly lower in IC patients than in female controls or females with UTIs: 0.50 +/- 0.06, 0.82 +/- 0.14. and 3.72 +/- 0.81 micromol. cyclic GMP/g. creatinine. CONCLUSIONS: Regulation of urinary NOS activity with subsequent changes in nitric oxide and cyclic GMP may be an important determinant of symptoms and immunologic responses to UTIs and IC.

Adolescent↗

Analysis of progressive change in automated visual fields in glaucoma.

PURPOSE: To detect and estimate the rate of progression of visual field loss in subjects with glaucoma who undergo long-term automated perimetric visual field testing. METHODS: Automated visual field data were obtained for subjects with glaucomatous visual field loss and a minimum of seven threshold field tests over at least 4.5 years. Univariate linear regression was performed with respect to mean deviation (MD), corrected pattern standard deviation (CPSD), mean thresholds of clusters corresponding to the Glaucoma Hemifield Test (GHT), and thresholds of 52 individual test locations. Subjects were classified as progressive or stable (unchanged or improved) based on the slope and statistical significance of these parameters. Adjusted P values were used to maintain the overall type 1 error at 5%. RESULTS: One hundred ninety-one subjects with a mean follow-up period of 7.1 years (range, 4.5 to 10.5 years) and a mean number of visual field tests of 9.5 (range, 7 to 16) were included. Twenty-four subjects (12.6%) showed progression in MD (mean slope [95% confidence interval], -1.26 [-1.50, -1.01] dB/year), and 27 (14.1%) showed progression in CPSD (mean slope [95% confidence interval], 0.71 [0.58, 0.84] dB/year). Thirty-five subjects (18.3%) had > or = 1 progressive GHT cluster. The mean slope in progressive clusters ranged from -1.51 [-1.82, -1.20] to -2.84 [-3.39, -2.29] dB/year. Thirty-six subjects (18.8%) had > or = 1 progressive individual test locations. Fifty-two subjects (27.2%) were classified as progressive based on progression of CPSD, > or = 1 cluster and/or > or = 1 point. CONCLUSIONS: Fewer than 1 in 3 subjects progressed by any one of the criteria for progression over an average of 7.1 years. Rates of progression that could be statistically confirmed were in the range of approximately 1 to 5 dB/year, depending on the number of fields, the variability over time, and the parameter assessed (global indices, GHT clusters, or individual points). No correlation between initial visual field status and the rate of progression was found. A minimum of approximately 5 years of follow-up with annual perimetry would be required to detect significant changes in the visual field by linear regression.

Adolescent↗

Quantitative trait locus for reading disability: correction.

In the news article "Can risky mergers save hospital-based research?" by Wade Roush (19 May, p. 968), the statement that University Hospitals of Cleveland rose from 20th in the rankings of teaching hospitals funded by the National Institutes of Health (NIH) in 1991 to 12th at present was incorrect. In fact, it was Case Western Reserve University (CWRU), with which University Hospitals of Cleveland is affiliated, that received $69 million in NIH grants in 1993, making it the 20th largest recipient of such grants among medical centers; the university then received $97 million in 1994, raising its rank to 12th. About $15 million of the increase, or 53%, was attributable to CWRU's 1992 affiliation with Henry Ford Hospital in Detroit. Other hospitals affiliated with Case Western include MetroHealth Medical Center, Mount Sinai Medical Center, St. Luke's Medical Center, and Cleveland Veterans' Affairs Medical Center.

Chromosome Mapping↗

Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53 gene.

The wild-type (wt) p53 tumor suppressor gene is commonly inactivated in human malignancies, either by mutations or by loss of expression. An additional proposed mechanism for inactivation of wt-p53 is amplification of the murine double minute 2 (MDM2) gene and overexpression of the MDM2 protein, which binds to p53 and eliminates its tumor suppressor function. To investigate a potential role for MDM2 in the inactivation of wt-p53 in pediatric acute lymphoblastic leukemia (ALL), we examined the expression of MDM2 and p53, as well as the occurrence of p53 mutations and possible amplification of the MDM2 gene, in 19 pediatric ALL cell lines and one pediatric acute myelogenous leukemia (AML) line. Although we did not find significant amplification of the MDM2 gene in any of the leukemic lines, we detected overexpression of MDM2 in all 10 lines that expressed wt-p53. Of the 10 lines without overexpression of the MDM2 gene, six (including the AML line) did not express p53, and four expressed mutant p53 with single point mutations in exons 7 and 8. To determine whether primary leukemic cells showed a similar correlation, we analyzed the original cryopreserved leukemic bone marrow cells from seven patients from whom cell lines were established. We obtained similar results from both the primary leukemic cells and the corresponding cell lines: overexpression of MDM2 was present in primary cells that expressed wt-p53 but not in cells that lacked expression of wt-p53. These findings suggest an important role for MDM2 in the pathogenesis of pediatric ALL in which leukemic cells express wt-p53.

Blotting, Southern↗

Postoperative selective bowel decontamination prevents gram-negative bacterial translocation in small-bowel graft recipients.

Gram-negative septic episodes are a potential risk of small-bowel transplantation; bacterial translocation through the graft is considered the mechanism. As a measure to prevent this complication, we evaluated postoperative selective bowel decontamination (SBD) in the rat model of orthotopic small-bowel transplantation [Lewis (LEW) and Brown-Norway (BN) rats as donors and recipients]. For 4 days after transplantation we gave FK 506, 2 mg/kg, which prevents rejection and results in indefinite recipient survival. For SBD, 24 mg/kg/day polymyxin E and 20 mg/kg/day tobramycin were administered via orogastric gavage to allograft recipients, both with and without FK 506 therapy. On Day 9, all rats were sacrificed, the peritoneal cavity was swabbed, and mesenteric lymph nodes (MLN), spleen, liver, and ileum were harvested for microbial qualitative and quantitative analysis. Animals with positive peritoneal swab cultures were excluded. SBD resulted in a significant reduction of the quantitative gram-negative bacterial flora in the ileum and cecum and of bacterial translocation to the MLN [0% versus 50% (no FK 506 therapy) and 8% versus 50% (FK 506 treated)]. In the allograft groups not treated with FK 506, SBD failed to significantly prolong survival, suggesting that acute rejection is not hastened by infection (bacterial translocation). We conclude that SBD in small-bowel-graft recipients prevents bacterial translocation by reducing intestinal gram-negative bacterial flora; this may reduce local and systemic infections by gut-derived organisms.

Animals↗

The protective role of enteral IgA supplementation in neonatal gut origin sepsis.

Preterm infants and infants unable to breast feed are particularly susceptible to gut origin sepsis. Many studies have shown the benefits of breast milk in decreasing the incidence of bacterial infections in neonates. Little in vivo work has focused on prevention of neonatal gut origin sepsis with breast milk components. The aim of this study was to determine whether supplementation of a standard neonatal formula with exogenous, luminally administered, human secretory IgA protects against gut origin sepsis in a newborn rabbit model. Sixty New Zealand white rabbit pups were delivered by cesarean section 1 day preterm and divided into two groups--the IgA group (n = 26) and the non-IgA group (n = 34). Animals were gavage-fed a standard artificial formula (KMR) twice daily. The IgA group was supplemented on days 3 and 4 with 6.25 mg/kg of human secretory IgA. The non-IgA group received an equal volume of saline. On the evening of day 3, the animals were orally challenged with Escherichia coli K100. The quantity of bacteria that colonized the cecum was similar in the two groups. The quantity of bacteria that translocated to the mesenteric lymph node, liver, and spleen was significantly lower in the IgA group (P < .05). The incidence of translocation to the organs was also significantly lower in the IgA group (P < .05). The exogenous secretory IgA showed specificity to E coli K100 by ELISA. These data show that neonatal formula supplemented with human secretory IgA decreases the incidence and quantity of bacterial translocation of E coli K100 in a neonatal rabbit model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Perioperative perspective of a United Nations humanitarian mission.

The use of deployable medical systems is not new to the US Army, but their use in support of United Nations peacekeepers is new. This article describes one Army unit's experience near Zagreb, Croatia, in 1993. The physical location, language and cultural barriers, and difficulty obtaining supplies posed significant challenges to those involved. The focus is on the OR team: its capabilities, achievements, and importance during this mission.

Adolescent↗

Protein quality of enteral nutrition products is consistent with label claims during shelf life and beyond expiration date.

OBJECTIVE: Eternal formulas were monitored during their shelf life and beyond expiration date to examine protein quality. DESIGN: Protein quality was determined by protein efficiency ratio (PER) bioassays and amino acid analyses. SETTING: A certified laboratory performed the PER tests according to procedures established by the Association of Official Analytical Chemists and recognized by the US Food and Drug Administration (FDA). The amino acid analyses were performed in our laboratory using validated methods. SAMPLES: Commercially available formulas (Ensure, Osmolite HN, TwoCal HN) that contained protein blends of caseinates or caseinates with soybean protein isolate were studied. MAIN OUTCOME MEASURES: Achievement of protein-quality values greater than or equal to 70% of the fresh reference casein value as determined by the PER method would be consistent with adequate protein quality as described by the FDA. Levels of indispensable amino acids that meet or exceed the standards established by the National Research Council of the National Academy of Sciences are considered high-quality proteins. Levels of amino acids throughout shelf life were compared with published label claims. RESULTS: Amino acid analyses, which included measurement of tryptophan and total sulfur amino acids, revealed that both fresh and outdated products met or exceeded standards for proteins of high biologic value and were consistent with label claims. The PER values ranged from 90% to 96% of the control diet for fresh product and 82% to 87% for products evaluated after expiration. CONCLUSION: The enteral products studied provide high-quality protein throughout the shelf life of the product.

Amino Acids↗

Consanguineous nuclear families used to identify a new locus for recessive non-syndromic hearing loss on 14q.

Hearing impairment is inherited most frequently as an autosomal recessive isolated clinical finding (non-syndromic hearing loss, NSHL). Extreme heterogeneity and phenotypic variability in the audiometric profile preclude pooling of affected families and severely hamper gene mapping by conventional linkage analysis. However, in instances of consanguinity, homozygosity mapping can be used to identify disease loci in small nuclear families. This report demonstrates the power of this technique by identifying a locus for recessive NSHL on 14q (DFNB4).

Chromosome Mapping↗

An autosomal recessive nonsyndromic form of sensorineural hearing loss maps to 3p-DFNB6.

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of congenitally acquired inherited hearing impairment. Although numerous loci are believed to exist, only five have been identified. Using a pooled genomic DNA screening strategy, we have identified a sixth locus, DFNB6, on 3p in the interval bounded by D3S1619 and D3S1766.

Alleles↗

The effects of whole-body vibration on human biodynamic response.

The objective of vibration research at the Armstrong Laboratory includes the expansion and improvement of the measurement, quantification, analysis, and modeling of human vibration response. The driving-point impedance and transmissibility techniques have been expanded and are rigorously applied in the research efforts. Driving-point impedance is defined as the ratio between the transmitted force and input velocity at the point of load application. Transmissibility is typically defined as the ratio between the acceleration level measured at some location on the body and the input acceleration at the seat. These two ratios are used to assess the magnitude and frequency location of resonance behaviors where maximum motions occur in the body. From these data, analytical models are developed which can simulate the motions and coupling behaviors, and predict the stiffness and damping characteristics of the affected anatomical structures. The ultimate goal of the research is to provide new and improved data and modeling capability for revising exposure standards and for developing equipment design guidelines and criteria for improving tolerance and reducing physiological consequences. This paper describes the results of recent studies conducted to identify the biodynamic behavior of major anatomical structures affected by seated whole-body vibration, to develop an analytical model for simulating human vibration response, and to apply the model to evaluate the effects of seat cushion materials on the transmission/attenuation pathways.

Acceleration↗