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Biomedical subjects

D Dean

Publications and source records attributed to D Dean.

At least 73 records · Page 4Linked to original sources
PubMed1998

Identification of Leptospira species in the pathogenesis of uveitis and determination of clinical ocular characteristics in south India.

Uveitis is considered a rare complication of leptospirosis. This report describes an epidemic of uveitis among patients with leptospirosis and provides data, using polymerase chain reaction (PCR) amplification of Leptospira DNA, that the pathogenesis is associated with anterior chamber spirochetes. Forty-six uveitis patients, 49 uveitis controls, and 54 cataract controls were enrolled at Aravind Eye Hospital (Madurai, India). Leptospiral DNA was detected by PCR of aqueous humor; serum antibody titers were determined by ELISA and microagglutination (MAT). Thirty-seven uveitis patients (80%) demonstrated leptospiral DNA compared with 5 controls (8%; P < .001). Thirty-three uveitis patients (72%) had positive serology compared with 10 uveitis controls (20%) and 13 cataract controls (24%; P < .001). This report describes the largest cluster of patients with leptospiral uveitis and identifies six clinical characteristics that provide a diagnostic profile for leptospiral uveitis. This profile will be important for determining treatment regimens in countries where PCR and MAT are not available.

Adolescent↗
PubMed1998

Chronic follicular conjunctivitis associated with Chlamydia psittaci or Chlamydia pneumoniae.

We determined whether patients with chronic conjunctivitis in whom direct fluorescent antibody (DFA) tests revealed genus-specific chlamydial antigens (but not species-specific Chlamydia trachomatis antigens) were infected with Chlamydia psittaci or Chlamydia pneumoniae. Patients were divided into a case group of possible non-trachomatis chlamydial conjunctivitis and a control group of nonchlamydial conjunctivitis on the basis of examination and DFA testing. Species-specific primers were used to amplify C. trachomatis, C. psittaci, and C. pneumoniae DNA with polymerase chain reaction (PCR). Four (27%) of 15 samples from the case group were positive for C. psittaci or C. pneumoniae DNA, whereas none of 24 control samples were positive. Sequencing revealed a C. pneumoniae, an avian C. psittaci, and two mammalian C. psittaci strains. A short course of oral antibiotic treatment appears to be inadequate for patients with non-trachomatis chlamydial conjunctivitis. Ocular infections due to C. pneumoniae and C. psittaci may be more common than previously recognized and can be identified by DFA and PCR.

Adult↗
PubMed1998

Average African American three-dimensional computed tomography skull images: the potential clinical importance of ethnicity and sex.

The production of average 'normative' three-dimensional (3D) computed tomography surface images of the bony skull has only recently been explored. The authors wish to determine the effect of using sex- and ethnicity-specific adult average 3D skull images for comparisons with patient images at various stages of craniofacial surgical management (i.e., diagnosis, treatment planning, prosthetic design, image-guided operative procedures, and outcomes assessment). Craniofacial surgical reconstruction for abnormal patterns of development, cancer resection, or trauma are most likely to benefit from these comparisons. To morphometrically test the significance of separating normative 3D skull data by sex and ethnicity, the authors collected 52 3D, anatomical landmarks from 3D computed tomography scans of dry skulls of 20 Americans of European ethnicity and 20 Americans of primarily African (i.e., primarily African and some European) ethnicity. A Procrustes-based morphometric analysis of shape detects 1.2 times as much interethnic variance as intersex variance. The African American sample presents 4.2% more dolichocephaly, wider orbits, flatter nasal area, larger gnathic anatomy, and more procumbent dentition. Pooling the sexes across both groups, it is seen that men tend to have less bulbous crania, more protruding brows, noses, and masticatory muscle attachments, and relatively less protrusive palettes and anterior mandibles. Despite a small sample size (N = 40), the authors' results are statistically significant (P approximately 0.001 overall) for both of the main factors, sex and ethnicity, separately.

Adolescent↗
PubMed1998

Validation of object-induced MR distortion correction for frameless stereotactic neurosurgery.

Spatial fidelity is a paramount issue in image guided neurosurgery. Until recently, three-dimensional computed tomography (3D CT) has been the primary modality because it provides fast volume capture with pixel level (1 mm) accuracy. While three-dimensional magnetic resonance (3D MR) images provide superior anatomic information, published image capture protocols are time consuming and result in scanner- and object-induced magnetic field inhomogeneities which raise inaccuracy above pixel size. Using available scanner calibration software, a volumetric algorithm to correct for object-based geometric distortion, and a Fast Low Angle SHot (FLASH) 3D MR-scan protocol, we were able to reduce mean CT to MR skin-adhesed fiducial marker registration error from 1.36 to 1.09 mm. After dropping the worst one or two of six fiducial markers, mean registration error dropped to 0.62 mm (subpixel accuracy). Three dimensional object-induced error maps present highest 3D MR spatial infidelity at the tissue interfaces (skin/air, scalp/skull) where frameless stereotactic fiducial markers are commonly applied. The algorithm produced similar results in two patient 3D MR-scans.

Algorithms↗
PubMed1998

Characterization of a strain of Chlamydia pneumoniae isolated from a coronary atheroma by analysis of the omp1 gene and biological activity in human endothelial cells.

Chlamydia pneumoniae is a respiratory pathogen that has been associated with chronic inflammatory diseases such as asthma and atherosclerosis. Recent isolation of C. pneumoniae from human carotid and coronary atheromas provides additional support for a role of this organism in atherogenesis. We characterized the coronary strain C. pneumoniae A-03 by sequence analysis of the major outer membrane protein gene (omp1). In addition, the in vitro activities of A-03 and three respiratory strains of C. pneumoniae (BAL-16, TW-183, and T-2634) were examined in infected human umbilical vein endothelial cells (HUVEC) by analysis of the production of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and soluble intercellular cell adhesion molecule 1 (sICAM-1). Sequence analysis of omp1 of C. pneumoniae A-03, compared to prototype strains TW-183 and AR-39, revealed five nucleotide changes resulting in nonsynonymous codons. Of interest was a nonconservative amino acid substitution (Ser to Pro) in position 61 of variable segment 1. In vitro, the extent of MCP-1, IL-8, and sICAM-1 production was dependent on the C. pneumoniae strain examined at low multiplicities of infection following 24 h of incubation. Strain A-03 displayed the lowest stimulatory activity in infected HUVEC, while T-2634 induced the highest levels of MCP-1, IL-8, and sICAM-1 among all strains examined. Heat-inactivated C. pneumoniae failed to stimulate production of these proteins by all strains tested. In contrast, only partial inhibition was observed by UV-inactivated organisms. Results from this study demonstrate that unlike prototype respiratory strains of C. pneumoniae, the coronary strain A-03 displays divergence in the omp1 gene. In addition, the stimulation of chemokines and adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by C. pneumoniae may be important in the pathogenesis of diseases associated with this organism, including atherosclerosis.

Amino Acid Sequence↗
PubMed1998

Comparison of performance and cost-effectiveness of direct fluorescent-antibody, ligase chain reaction, and PCR assays for verification of chlamydial enzyme immunoassay results for populations with a low to moderate prevalence of Chlamydia trachomatis infection.

Many laboratories use a commercial enzyme immunoassay (EIA) with verification testing to diagnose Chlamydia trachomatis infections in an effort to contain costs. This study was designed to compare the performance and cost-effectiveness of direct fluorescent-antibody assay (DFA), commercial PCR, and ligase chain reaction (LCR) for the verification of EIA results. Cervical specimens were screened by EIA. DFA, PCR, and LCR were compared as verification tests for EIA-reactive specimens and negative greyzone (NGZ) specimens at 50% below the cutoff value. These samples were also tested by in-house PCR, which was used in the analysis of verification results. A total of 477 (7%) of 6,571 samples were reactive or within the NGZ. EIA results with verification by DFA testing (EIA/DFA results) agreed with 93% of the true results compared with 97% for EIA/PCR results for one set of 242 samples; there was 97% agreement with true results for EIA/DFA results versus 95% for EIA/LCR results for another set of 235 samples. Ten samples were false positive by LCR. Time and costs were equivalent for EIA with the DFA, PCR, or LCR as the verification test but were two- to threefold greater for PCR or LCR alone than for EIA with verification. Since it is important to balance cost containment with public health objectives, DFA, PCR, and LCR as EIA verification tests for cervical samples offer acceptable sensitivities and specificities at reasonable cost for low- to moderate-risk populations and therefore can be extended to a broader spectrum of at-risk populations.

Adolescent↗
PubMed1998

16S ribosomal DNA typing for identification of pathogens in patients with bacterial keratitis.

The identification of pathogens in patients with bacterial keratitis remains problematic because standard diagnostic tests are negative for 40 to 60% of patients. A cross-sectional study was undertaken to determine if PCR and sequence analysis of 16S ribosomal DNA (rDNA) could be used to detect bacterial pathogens in patients with keratitis. Corneal specimens were collected for culture and rDNA typing. Variable segments of each rDNA specimen were amplified by PCR, sequenced, and aligned with the sequences in GenBank. Eleven patients had microbiologically documented bacterial keratitis, while 17 patients had keratitis due to other causes. Nine (82%) of 11 bacterial keratitis patients were PCR positive; each sequencing result matched the culture results. Seventeen (100%) patients with nonbacterial keratitis were PCR negative. Our data suggest that 16S rDNA typing holds promise as a rapid alternative to culture for identifying pathogens in patients with bacterial keratitis.

Adult↗
PubMed1998

Conjunctival impression cytology for vitamin A deficiency in the presence of infectious trachoma.

BACKGROUND/AIMS: Increased morbidity and mortality from a number of infectious diseases have been associated with vitamin A deficiency. Trachoma and vitamin A deficiency are both important causes of blindness in Nepal. The purpose of this study was to determine the association between the diagnosis of vitamin A deficiency by conjunctival impression cytology and the diagnosis of infectious trachoma by the polymerase chain reaction (PCR) in the Lumbini zone of Nepal. METHODS: 70 children under the age of 11 in a rural village in the Lumbini zone were examined for clinical evidence of active trachoma. The conjunctiva of each child was tested for ocular Chlamydia trachomatis infection using PCR, and for loss of goblet cells (a sign of subclinical vitamin A deficiency) using conjunctival impression cytology. RESULTS: The presence of infectious trachoma was associated with the loss of goblet cells on conjunctival impression cytology (p = 0.02). This relation was present and significant even when adjusted for age (p = 0.05) and degree of inflammation (p = 0.02). In fact, even subclinical infection with chlamydia was associated with an abnormal conjunctival impression cytology (p = 0.02). CONCLUSIONS: Children with infectious trachoma are significantly more likely to have an abnormal conjunctival impression cytology, even if the infection is subclinical. Thus, the diagnosis of vitamin A deficiency from conjunctival impression cytology alone should be made with some caution in areas with endemic trachoma. Further studies will be needed to determine the cause of this association.

Child↗
PubMed1998

Malonyl CoA, long chain fatty acyl CoA and insulin resistance in skeletal muscle.

Malonyl CoA is an inhibitor of carnitine palmitoyl transferase 1 (CPT1), the enzyme that regulates the transfer of long chain fatty acyl CoA into mitochondria. By virtue of this effect, it is thought to play a key role in regulating fatty acid oxidation. Thus, when the supply of glucose to muscle is increased, malonyl CoA levels increase in keeping with a decreased need for fatty acid oxidation, and fatty acids are preferentially esterified to form diaglycerol and triglycerides. In contrast, during exercise, when the need for fatty acid oxidation is increased, malonyl CoA levels fall. Changes in glucose supply regulate malonyl CoA by modulating the concentration of cytosolic citrate, an allosteric activator of acetyl CoA carboxylase (ACC), the rate-limiting enzyme for malonyl CoA formation and a precursor of its substrate cytosolic acetyl CoA. Conversely, exercise lowers the concentration of malonyl CoA, by activating an AMP-activated protein kinase, which phosphorylates and inhibits ACC. A number of reports have linked sustained increases in the concentration of malonyl CoA in muscle to insulin resistance. In this paper, we review these reports, as well as the notion that changes in malonyl CoA contribute to the increases in long chain fatty acyl CoA, (LCFA CoA), diacylglycerol and triglyceride content and changes in protein kinase C activity and distribution observed in insulin-resistant muscle. We also review the implications of the malonyl CoA/LCFA CoA hypothesis to two other proposed mechanisms for insulin resistance, the glucose-fatty acid cycle and the hexosamine theory.

Acyl Coenzyme A↗
PubMed1997

Efficacy of OKT3 as primary therapy for histologically confirmed acute renal allograft rejection.

BACKGROUND: OKT3 is often used as primary treatment for acute renal allograft rejection. In a retrospective study, we sought to determine the efficacy of OKT3 as a first-line agent in reversing histologically confirmed acute renal allograft rejection. METHODS: Patients with mild to moderate, moderate, or severe acute cellular and acute vascular rejection who had not received any other anti-rejection treatment were included in this analysis. A total of 88 patients, who received OKT3 between 1987 and 1995, fulfilled these criteria. RESULT: Seventy of these patients were renal transplant recipients, and 18 were combined kidney and pancreas transplant recipients. The median time to the diagnosis of rejection from transplantation was 32 days (range, 6 days to 13 years). On histology, 6 were graded as mild to moderate, 36 as moderate, 29 as moderate to severe, and 17 as severe rejection. The mean baseline serum creatinine was 1.62 mg/dl (range, 0.7-10.1 mg/dl), and the mean serum creatinine at the time of diagnosis of rejection was 2.60 mg/dl (range, 1.4-12.7 mg/dl) (P=<0.0001). The mean duration of OKT3 treatment was 11.2 days (range, 8-18 days). The mean serum creatinine at the end of OKT3 treatment was 1.73 mg/dl (range, 0.6-5.0 mg/dl; P=0.24 compared with baseline serum creatinine). Rejection was reversed in 86 (98%) patients. Graft survival at 1 year after OKT3 therapy was 87.5% (77 of 88). At a mean follow-up of 38 months, 8 patients had died and 26 grafts were lost. The mean serum creatinine level in the 64 patients with a functioning graft was 1.76 mg/dl (range, 0.8-4.0 mg/dl) at the last follow-up. CONCLUSION: OKT3 when utilized as first-line therapy reversed 98% of the acute rejection episodes, with a 1-year post-OKT3 graft survival of 87.5%.

Acute Disease↗
PubMed1997

Molecular and mutation trends analyses of omp1 alleles for serovar E of Chlamydia trachomatis. Implications for the immunopathogenesis of disease.

Serovars E, F, and D are the most prevalent Chlamydia trachomatis strains worldwide. This prevalence may relate to epitopes that enhance infectivity and transmission. There are numerous major outer membrane protein (MOMP) gene (omp1) variants described for D and F but few for E. However, omp1 constant regions are rarely sequenced yet, they may contain mutations that affect the structure/function relationship of the protein. Further, differentiating variants that occur as a result of selection from variants that contain random mutations without biologic impact is difficult. We investigated 67 urogenital E serovars and found 11 (16%) variants which contained 16 (53%) nonconservative amino acid changes. Using signature-pattern analysis, 57 amino acids throughout MOMP differentiated the E sequence set from the non-E sequence set, thus defining E strains. Four E variants did not match this signature-pattern, and, by phenetic analyses, formed new phylogenetic branches, suggesting that they may be biologically distinct variants. Our analyses offer for the first time a unique approach for identifying variants that may occur from selection and may affect infectivity and transmission. Understanding the mutation trends, phylogeny, and molecular epidemiology of E variants is essential for designing public health control interventions and a vaccine.

Alleles↗
PubMed1997

Uveitis associated with an epidemic outbreak of leptospirosis.

PURPOSE: To define uveitis associated with leptospirosis in a clinical setting. METHODS: We present the clinical features of 73 consecutive cases of uveitis linked clinically to an outbreak of systemic leptospirosis in patients with antibodies to Leptospira species who were examined from January to September 1994. RESULTS: In 73 patients, the pattern of ocular involvement was unilateral in 35 and bilateral in 38. Panuveitis was seen in 106 eyes (95.5%), retinal periphlebitis in 57 eyes (51.4%), and hypopyon in 14 eyes (12.6%). Anterior uveitis alone without hypopyon was observed in three eyes (2.7%), whereas vitreous inflammatory reaction alone was seen in two eyes (1.8%). Sixty of 73 patients (82.2%) or 91 of 111 eyes (82.0%) were followed up for 8 months. Final visual acuity was 6/6 (20/20) in 47 eyes (52%) and improved during treatment, although not up to 6/6, in 15 eyes (16%). Twenty-eight eyes (31%) maintained same vision, and one eye showed deterioration of vision. CONCLUSION: Uveitis associated with leptospirosis may manifest as unilateral or bilateral uveitis, anterior uveitis, or panuveitis. The prognosis is generally good in this entity, even when the inflammation is severe. Awareness of this disease in endemic areas is important in order to differentiate it from other uveitic entities, especially in young male patients in whom other immunologic uveitides are also common.

Adult↗
PubMed1997

The basement membrane zone in lichen sclerosus: an immunohistochemical study.

The alteration in expression of basement membrane zone (BMZ) components in lichen sclerosus was investigated by immunohistochemical staining of skin biopsies from seven patients with histologically confirmed disease compared with controls. Monoclonal antibodies and polyclonal sera directed against proteins of the hemidesmosomes, anchoring fibrils, lamina lucida, lamina densa and BMZ collagens were used. Characteristic histological appearances at the dermo-epidermal junction were reflected in widespread alterations in antigen expression in the epidermal basement membrane and the papillary dermis. Expression of the proteins which constitute the structural scaffold (collagen IV and VII) were increased in lichen sclerosus. Expression of hemidesmosomal proteins which mediate adhesion and cell to matrix interaction (alpha 6 beta 4 and bullous pemphigoid antigen) and expression of anchoring filament components were markedly reduced, suggesting that the epidermal cells are exposed to selective damage.

Antibodies, Monoclonal↗
PubMed1997

Changes in CD44 isoform expression during inflammatory skin disease.

The CD44 family of cell surface glycoproteins is widely expressed in epithelial, mesothelial and haemopoietic tissues and is thought to function primarily as adhesion molecules. The molecule has an intracellular, a transmembrane and an extracellular domain. The membrane proximal region of the extracellular domain is of variable structure depending on which of 10 variable exons are involved in coding for this region. Both in vitro stimulated T cells and cytokine stimulated keratinocytes are known to express certain isoforms. In this study we have investigated whether specific isoforms of the CD44 molecule are expressed on epithelial cells and lymphocytes in the course of two inflammatory skin diseases, namely lupus erythematosus and lichen planus. Monoclonal antibodies, specific to the epitopes of the CD44 molecule encoded by v3, v4/5, v6 and v8/9 variable exons and a pan CD44 marker, were used on 10 lupus and 8 lichen planus frozen skin samples and compared with normal skin from 9 different body sites. Results failed to show detectable levels of variant isoforms of CD44 on lymphocytes in either inflammatory skin disease, despite evidence of T cell activation. All CD44 variant isoforms were reduced on the keratinocytes in some sections of lupus and lichen planus. The results are discussed in the context of the current models for the role of CD44 in the immune response.

Humans↗
PubMed1996

Genetic factors for the development of Alzheimer disease in the Cherokee Indian.

OBJECTIVE: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. DESIGN: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. RESULTS: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age.

Aged↗
PubMed1996

Orally active inhibitors of human leukocyte elastase. I. Disposition of L-683,845 in rats and rhesus monkeys.

L-683,845 is an orally active inhibitor of human leukocyte elastase. Its disposition was studied in rats and rhesus monkeys after dosing with a 3H- or 14C-labeled compound intravenously at 5 mg/kg and orally at 10 mg/kg. L-683,845 exhibited different pharmacokinetics in these two species. In rats, L-683,845 was well-absorbed after oral dosing, with a maximum concentration of 6 microg/ml at 2 hr and bioavailability of approximately 100%. After intravenous dosing, it was cleared slowly at approximately 3 ml/min/kg, with a terminal half-life of approximately 7 hr and a volume of distribution at steady-state of 1 liter/kg. After both intravenous and oral dosing, L-683,845 comprised 50-95% of plasma radioactivity. About 75% of the intravenous and 87% of the oral dose were recovered in the feces as parent and/or conjugates, with the remaining fraction recovered in the urine as polar components. In rhesus monkeys, maximum concentration after oral dosing was only 0.25 microg/ml, and bioavailability was 50%. Plasma clearance was 8-fold higher, at 23 ml/min/kg, and volume of distribution at steady-state larger, at 2 liters/kg, than in rats. The terminal half-life of L-683,845 could not be determined accurately after intravenous dosing, but seemed to be long in orally dosed animals, approximately 13 hr. Intact L-683,845 was a minor component in plasma comprising only approximately 20% of the radioactivity at most time points. Moreover, persistent levels of radioactivity were detected in plasma and urine of rhesus monkeys even at 1-month postdose, and > or = 25% of the radioactivity in plasma was irreversibly bound to proteins at the later time points. Recovery of the radioactivity was incomplete, with only 77% of the intravenous and 43% of the oral dose recovered over a 4-day period. L-683,845-derived radioactivity distributed to all major rat tissues, with highest levels in the liver followed by the small intestine, adrenals, kidneys, and lungs. Radioactivity concentrations in the liver were high even at 24 hr, 22.7 microg eq/g. A large portion of the intravenous dose was recovered in the small intestine, approximately 40% at 2 hr, indicating rapid and extensive biliary excretion. L-683,845 was metabolized primarily to the acyl glucuronide, which was very unstable in rat plasma, and was subject to hydrolysis to L-683,845 and rearrangement. The glucuronide and L-683,845 were degraded in rat plasma by opening the beta-lactam ring and loss of the C4 substituent followed by decarboxylation to give an olefin and/or decomposition to the monosubstituted urea. Based on inhibition by organophosphorus compounds, it is speculated that their degradation is catalyzed by a type B esterase.

Animals↗