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1.
J Dairy Sci ; 102(10): 8874-8882, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31351719

ABSTRACT

The objectives of this study were to determine the effects of the weaning transition and supplemental rumen-protected butyrate on subacute ruminal acidosis, feed intake, and growth parameters. Holstein bull calves (n = 36; age = 10.7 ± 4.1 d; ± standard deviation) were assigned to 1 of 4 treatment groups: 2 preweaning groups, animals fed milk replacer only (PRE-M) and those fed milk replacer, calf starter, and hay (PRE-S); and 2 postweaning groups, animals fed milk replacer, calf starter, and hay without supplemental rumen-protected butyrate (POST-S) or with supplemental rumen-protected butyrate at a rate of 1% wt/wt during the 2-wk weaning transition (POST-B). Milk replacer was provided at 1,200 g/d; starter, water, and hay were provided ad libitum. Weaning took place over 14 d by reducing milk replacer provision to 900 g/d in wk 7, 600 g/d in wk 8, and 0 g/d in wk 9. Rumen pH was measured continuously for 7 d during wk 6 for PRE-S and PRE-M and during wk 9 for POST-S and POST-B. After rumen pH was measured for 7 d, calves were euthanized, and rumen fluid was sampled and analyzed for volatile fatty acid (VFA) profile. Individual feed intake was recorded daily, whereas, weekly, body weights were recorded, and blood samples were collected. Compared with PRE-M, PRE-S calves tended to have a greater total VFA concentration (35.60 ± 11.4 vs. 11.90 ± 11.8 mM) but mean rumen pH was unaffected (6.25 ± 0.22 vs. 6.17 ± 0.21, respectively). Between PRE-S (wk 6) and POST-S (wk 9), calf starter intake increased (250 ± 219 vs. 2,239 ± 219 g/d), total VFA concentrations increased (35.6 ± 11.4 vs. 154.4 ± 11.8 mM), but mean rumen pH was unaffected (6.25 ± 0.22 vs. 6.40 ± 0.22, respectively). Compared with POST-S, POST-B calves had greater starter intake in wk 7, 8, and 9, but POST-B tended to have lower total VFA concentration (131.0 ± 11.8 vs. 154.4 ± 11.8 mM) and lower mean ruminal pH (5.83 ± 0.21 vs. 6.40 ± 0.22). In conclusion, the weaning transition does not appear to affect rumen pH and VFA profile, but supplementing rumen-protected butyrate during the weaning transition increased starter intake and average daily gain. Further, these data suggest that the ability of the rumen to manage rumen pH changes fundamentally postweaning. Why weaned calves with lower rumen pH can achieve higher calf starter intakes is unclear; these data suggest the effect of rumen pH on feed intake differs between calves and cows.


Subject(s)
Animal Feed , Butyrates/pharmacology , Diet/veterinary , Rumen/drug effects , Weaning , Animal Feed/analysis , Animals , Body Weight , Cattle , Fatty Acids, Volatile/metabolism , Fermentation , Male , Milk , Rumen/metabolism
2.
Psychol Med ; 45(10): 2111-22, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25652023

ABSTRACT

BACKGROUND: Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted body image and are frequently co-morbid with each other, although their relationship remains little studied. While there is evidence of abnormalities in visual and visuospatial processing in both disorders, no study has directly compared the two. We used two complementary modalities--event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI)--to test for abnormal activity associated with early visual signaling. METHOD: We acquired fMRI and ERP data in separate sessions from 15 unmedicated individuals in each of three groups (weight-restored AN, BDD, and healthy controls) while they viewed images of faces and houses of different spatial frequencies. We used joint independent component analyses to compare activity in visual systems. RESULTS: AN and BDD groups demonstrated similar hypoactivity in early secondary visual processing regions and the dorsal visual stream when viewing low spatial frequency faces, linked to the N170 component, as well as in early secondary visual processing regions when viewing low spatial frequency houses, linked to the P100 component. Additionally, the BDD group exhibited hyperactivity in fusiform cortex when viewing high spatial frequency houses, linked to the N170 component. Greater activity in this component was associated with lower attractiveness ratings of faces. CONCLUSIONS: Results provide preliminary evidence of similar abnormal spatiotemporal activation in AN and BDD for configural/holistic information for appearance- and non-appearance-related stimuli. This suggests a common phenotype of abnormal early visual system functioning, which may contribute to perceptual distortions.


Subject(s)
Anorexia Nervosa/physiopathology , Body Dysmorphic Disorders/physiopathology , Perceptual Distortion , Visual Perception , Adolescent , Adult , Anorexia Nervosa/complications , Anorexia Nervosa/diagnosis , Anorexia Nervosa/psychology , Body Dysmorphic Disorders/complications , Body Dysmorphic Disorders/diagnosis , Body Dysmorphic Disorders/psychology , Evoked Potentials , Female , Humans , Los Angeles , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Psychiatric Status Rating Scales , Vision Disorders/complications , Vision Disorders/physiopathology , Young Adult
3.
Arthritis Rheum ; 64(1): 285-96, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22031171

ABSTRACT

OBJECTIVE: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. METHODS: A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. RESULTS: Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. CONCLUSION: Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.


Subject(s)
Anticholesteremic Agents/therapeutic use , Atherosclerosis/prevention & control , Heptanoic Acids/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Pyrroles/therapeutic use , Adolescent , Atherosclerosis/complications , Atherosclerosis/diagnosis , Atorvastatin , Carotid Intima-Media Thickness , Child , Disease Progression , Double-Blind Method , Female , Humans , Lipids/blood , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Male , Treatment Outcome , Young Adult
4.
Lupus ; 19(11): 1315-25, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20861207

ABSTRACT

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.


Subject(s)
Biomarkers/blood , Cardiovascular Diseases , Lupus Erythematosus, Systemic , Adolescent , C-Reactive Protein/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Child , Cholesterol/blood , Cross-Sectional Studies , Double-Blind Method , Female , Humans , Lipoprotein(a)/blood , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Placebos , Risk Factors , Triglycerides/blood , Young Adult
5.
Genes Immun ; 10(5): 446-56, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19440200

ABSTRACT

In our earlier study, we utilized a Bayesian design to probe the association of approximately 1000 genes (approximately 10,000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.


Subject(s)
Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide , Age of Onset , Bayes Theorem , Case-Control Studies , Genome-Wide Association Study , Humans , Lupus Erythematosus, Systemic/epidemiology
6.
J Cell Biol ; 103(6 Pt 1): 2541-50, 1986 Dec.
Article in English | MEDLINE | ID: mdl-3536968

ABSTRACT

Using monoclonal antibodies to the plant photoreceptor, phytochrome, we have investigated by immunogold electron microscopy the rapid, red light-induced, intracellular redistribution (termed "sequestering") of phytochrome in dark-grown Avena coleoptiles. Pre-embedding immunolabeling of 5-micron-thick cryosections reveals that sequestered phytochrome is associated with numerous, discrete structures of similar morphology. Specific labeling of these structures was also achieved by post-embedding ("on-grid") immunostaining of LR-White-embedded tissue, regardless of whether the tissue had been fixed chemically or by freeze substitution. The phytochrome-associated structures are globular to oval in shape, 200-400 nm in size, and are composed of amorphous, granular material. No morphologically identifiable membranes are present either surrounding or within these structures, which are often present as apparent aggregates that approach several micrometers in size. An immunogold labeling procedure has also been developed to identify the particulate, subcellular component with which phytochrome is associated in vitro as a consequence of irradiation of Avena coleoptiles before their homogenization. Structures with appearance similar to those identified in situ are the only components of the pelletable material that are specifically labeled with gold. We conclude that the association of phytochrome with these structures in Avena represents the underlying molecular event that ultimately is expressed both as red light-induced sequestering in vivo and enhanced pelletability of phytochrome detected in vitro.


Subject(s)
Phytochrome/metabolism , Plant Proteins/metabolism , Plants/ultrastructure , Antibodies , Antibodies, Monoclonal , Antigen-Antibody Complex , Darkness , Fluorescent Antibody Technique , Gold , Light , Microscopy, Electron , Plants/metabolism
7.
Leuk Res ; 31(1): 33-7, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16806467

ABSTRACT

Leukemia-associated antigens such as proteins encoded by MAGE genes might provide tools for immunotherapy of leukemia. Positive and negative results of MAGE-A gene expression in hematological malignancies have been reported. This led us to study MAGE-A gene expression in human leukemias using RT-PCR. Among 115 leukemias from various subtypes, 14/34 (41.17%) AML were positive for one of the three genes analyzed (MAGE-A1 1/32; MAGE-A3 10/32; MAGE-B2 3/12). Expression was also detected in 23/76 (30.26%) B-cell ALL patients (MAGE-A1 2/53; MAGE-A3 20/53; MAGE-B2 1/32). One of these patients expressed both MAGE-A1 (weak signal) and -A3 (strong signal) genes. Other patient with CML were positive for MAGE-B2 (1/5, 20%). MAGE-A3 expression data were corroborated by real time RT-PCR through determination of MAGE-A3 transcript levels. We concluded that the MAGE-A3 gene is expressed at the mRNA level in a proportion of human leukemias.


Subject(s)
Antigens, Neoplasm/genetics , Leukemia/genetics , Neoplasm Proteins/genetics , RNA, Messenger/genetics , Transcription, Genetic , Adult , Antigens, Neoplasm/blood , Base Sequence , DNA Primers , Female , Gene Amplification , Humans , Leukemia/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Neoplasm Proteins/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Reverse Transcriptase Polymerase Chain Reaction
8.
J Med Chem ; 42(19): 3994-4000, 1999 Sep 23.
Article in English | MEDLINE | ID: mdl-10508447

ABSTRACT

Syntheses of several carbamate analogues of 2, 5-bis(4-amidinophenyl)furan (1) under mild conditions and their evaluation as prodrugs against Pneumocystis carinii pneumonia (PCP) in an immunosuppressed rat model are described. Thus, nine new bis-carbamates: methoxycarbonyl (2), 2,2,2-trichloroethoxycarbonyl (3), ethylthiocarbonyl (4), benzyloxycarbonyl (5), (4-methyl-2-oxo-1, 3-dioxol-4-en-5-yl)methoxycarbonyl (6), phenoxycarbonyl (7), 4-fluorophenoxycarbonyl (8), 4-methoxyphenoxycarbonyl (9), and (1-acetoxy)ethoxycarbonyl (10) and a bis-carbonate ethoxycarbonyloxy (11) of the bis-amidine 1 have been synthesized and evaluated. The in vivo results show that the 4-fluorophenyl carbamate 8 and the 4-methoxyphenyl carbamate 9 in this series had the best anti-PCP activity by both intravenous and oral administration at a dosage level of 22 mol and 33 micromol/kg/day, respectively. Compounds 3-7 were also more active than the parent drug (1) on oral administration. The acute toxicity usually exhibited by the parent amidine 1 at a dosage level of 22 micromol/kg/day on intravenous administration has been significantly reduced by the prodrug modifications, with the exception of compound 10 which exhibited some toxicity. This report also describes the synthesis of several aryl-alkyl and aryl-aryl carbonates (12-14, 16-23) as efficient reagents for the preparation of carbamate derivatives from bis-arylamidines.


Subject(s)
Antifungal Agents/chemical synthesis , Benzamidines/chemistry , Carbamates/chemistry , Pneumocystis/drug effects , Prodrugs/chemical synthesis , Administration, Oral , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacology , Benzamidines/administration & dosage , Benzamidines/pharmacology , Models, Chemical , Prodrugs/administration & dosage , Prodrugs/pharmacology , Rats
9.
J Med Chem ; 41(20): 3872-8, 1998 Sep 24.
Article in English | MEDLINE | ID: mdl-9748362

ABSTRACT

The syntheses of nine new derivatives of 2, 5-bis[4-(N-alkylamidino)phenyl]furans with extended aromatic systems are reported. The interaction of these dicationic furans with poly(dA)poly(dT) and with the duplex oligomers d(CGCGAATTCGCG)2 and d(GCGAATTCGC)2 was determined by Tm measurement, and the effectiveness of these compounds against the immunosuppressed rat model of Pneumocystis carinii was evaluated. At a screening dose of 10 micromol/kg, 4 of the 12 amidino furans described here are more active than the parent compound 1. In general, extension of the aromatic system in the absence of a substitution of the amidino nitrogens resulted in higher affinity for DNA than the parent compound as judged by the larger DeltaTm values and suggests enhanced van der Waals interactions in the amidino furan-DNA complex. Three of the compounds, 3, 5, and 11, yield cysts counts of less than 0.1% of control when administered at a dosage of 10 micromol/kg. Compound 3, which does not have an extended aromatic system, is the most active derivative. Although a direct correlation between anti-P. carinii activity and DNA binding affinity was not observed, all compounds which have significant activity have large DeltaTm values.


Subject(s)
Amidines/chemical synthesis , Antifungal Agents/chemical synthesis , Furans/chemical synthesis , Amidines/chemistry , Amidines/metabolism , Amidines/pharmacology , Animals , Antifungal Agents/chemistry , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Drug Evaluation, Preclinical , Furans/chemistry , Furans/metabolism , Furans/pharmacology , Immunosuppression Therapy , Oligodeoxyribonucleotides/metabolism , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/immunology , Poly dA-dT/metabolism , Protein Binding , Rats , Structure-Activity Relationship
10.
J Med Chem ; 42(12): 2260-5, 1999 Jun 17.
Article in English | MEDLINE | ID: mdl-10377232

ABSTRACT

Dicationic 2,4-bis(4-amidinophenyl)furans 5-10 and 2, 4-bis(4-amidinophenyl)-3,5-dimethylfurans 14 and 15 have been synthesized. Thermal melting studies revealed high binding affinity of the compounds to poly(dA-dT) and to the duplex oligomer d(CGCGAATTCGCG)2. All of the new compounds were effective against Pneumocystis carinii pneumonia in the immunosuppressed rat model with up to 200-fold increase in activity compared to the control compound pentamidine. No toxicity was noted for 5, 7-10 at the dose of 10 micromol/kg/d; however, the isopropyl analogue 7 showed toxicity comparable to pentamidine at the dosage of 20 micromol/kg/d. Dimethylation of the parent compound on the furan ring resulted in reduced activity and increased toxicity.


Subject(s)
Amidines/chemical synthesis , Antifungal Agents/chemical synthesis , Furans/chemical synthesis , Pneumonia, Pneumocystis/drug therapy , Amidines/chemistry , Amidines/pharmacology , Amidines/toxicity , Animals , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/toxicity , DNA/chemistry , Furans/chemistry , Furans/pharmacology , Furans/toxicity , Immunocompromised Host , Rats , Structure-Activity Relationship
11.
J Med Chem ; 41(1): 124-9, 1998 Jan 01.
Article in English | MEDLINE | ID: mdl-9438029

ABSTRACT

The syntheses of 12 new 2,5-bis[4-(N-alkylamidino)phenyl]furans are reported. The interaction of these dicationic furans with poly(dA-dT) and with the duplex oligomer d(CGCGAATTCGCG)2 was determined by Tm measurements, and the effectiveness of these compounds against the immunosuppressed rat model of Pneumocystis carinii was evaluated. At the screening dose of 10 mumol/kg, 9 of the 14 N-alkylamidino furans described here are more active than the parent compound 1. Substitution of an alkyl group of the amidino nitrogen, except for in 9, 13, and 15, resulted in higher affinity for DNA than the parent compound as judged by the larger delta Tm values and suggests enhanced van der Waals interactions in the bis-amidine-DNA complex. Five of the compounds, 3, 5, 7, 10, and 12, yield cyst counts of less than 0.1% of control when administered at a dosage of 10 mumol/kg. Five compounds, 1, 6, 8, 10, and 12, show significant activity at a dosage of approximately 1 mumol/kg; 12 is the most active derivative, and it is approximately 100 times more effective than pentamidine in this animal model.


Subject(s)
Anti-Infective Agents/chemical synthesis , Furans/chemical synthesis , Pneumocystis/drug effects , Pneumonia, Pneumocystis/drug therapy , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/therapeutic use , Base Sequence , Binding Sites , Furans/chemistry , Furans/therapeutic use , Microchemistry , Oligodeoxyribonucleotides/chemistry , Poly dA-dT/chemistry , Rats
12.
Pediatrics ; 83(2): 235-9, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2913553

ABSTRACT

To evaluate whether the onset of systemic lupus erythematosus in the first decade of life was associated with a unique pattern of racial preponderance, sexual preponderance, genetic predisposition, or disease expression, the medical records of 23 children with systemic lupus erythematosus prior to their tenth birthdays were compared with the medical records of 82 children in whom lupus was diagnosed between their tenth and 20th birthdays. No statistically significant differences in sex distribution, racial (ethnic) background, family history, mode of onset, morbidity, or mortality rates were found between the two age groups. The frequently held view that children with early-onset lupus do worse probably relates to the fact that even though they survive as long as children with the older-onset disease, they die younger because they have the onset of their lupus at a younger age.


Subject(s)
Lupus Erythematosus, Systemic/physiopathology , Adolescent , Adult , Age Factors , Child , Child, Preschool , Ethnicity , Female , Humans , Kidney Diseases/physiopathology , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/mortality , Male , Prognosis , Racial Groups , Sex Factors
13.
Pediatrics ; 89(2): 240-6, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1734390

ABSTRACT

As newer treatment modalities become available for patients with severe lupus nephritis, it becomes increasingly important to identify patients at risk for renal failure. In this study, the records of 90 children presenting with systemic lupus erythematosus over a 13-year period were reviewed. Nineteen were lost to follow-up prior to completion of the study. Of the 71 remaining children, 16 (22%) progressed to chronic renal failure. Persistent hypertension lasting greater than 4 months, anemia, abnormalities of the urinalysis, and elevated serum creatinine level were significantly associated with progression to renal failure. Sex, race, age, abnormalities of creatinine clearance, and 24-hour urine protein collection were not associated with progression to renal failure. Renal biopsies were obtained in 45 children. Biopsies were initially classified according to World Health Organization criteria. Diffuse proliferative glomerulonephritis was significantly associated with progression to renal failure. The 45 biopsies available were reviewed by one of the authors and categorized by activity and chronicity indices. Both the active lesions of fibrinoid necrosis, synechiae, tubular casts, and vasculitic lesions and the chronic lesion of glomerular sclerosis correlated with progression to renal failure. Of the 16 children who progressed to renal failure, 2 had cadaver kidney transplants and are well 5 years posttransplant; 4 had fulminant lupus and died within 1 month of commencing dialysis; 10 began chronic dialysis. Five of the 10 children on chronic dialysis died from sepsis. These data suggest that children with systemic lupus erythematosus who undergo dialysis do poorly.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Kidney Failure, Chronic/epidemiology , Lupus Nephritis/epidemiology , Biopsy , Child , Female , Humans , Kidney/pathology , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/therapy , Life Tables , Lupus Nephritis/pathology , Lupus Nephritis/therapy , Male , Prognosis , Risk Factors , Survival Analysis
14.
Int J Parasitol ; 29(7): 1001-9, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10501610

ABSTRACT

We tested two hypotheses concerning changes in investment in current reproduction for parasitised hosts, using amphipods (Corophium volutator) which act as second intermediate hosts for trematodes (Gynaecoyla aduncta). One hypothesis requires that parasites exert control over their hosts (parasite manipulation), whereas the other predicts that hosts control decisions over investment (adaptive host response). Although these hypotheses are viewed as mutually exclusive, our various results support both hypotheses. For example, female amphipods infected by late-stage larvae were often found crawling at times when predation by sandpipers (Calidris pusilla), which are the final hosts for trematodes, was likely, while uninfected females typically remained in their burrows. Furthermore, old females that were newly-infected by trematodes often aborted and ate their young. Both of these responses seem inconsistent with female investment in current reproduction, but can be interpreted as adaptive parasite manipulation. In contrast, young non-ovigerous females that were newly-infected hastened the onset of their parturial moult and thus, time to becoming receptive. This response can be explained as a host adaptation to minimise the cost of parasites. We contend that differences between parasitised and unparasitised hosts in behaviour or investment can be explained as both parasite and host adaptations, expressed at different times in the host's life history. Such compromise will help explain the persistence of parasite-host associations in nature.


Subject(s)
Adaptation, Physiological , Crustacea/physiology , Crustacea/parasitology , Trematoda/growth & development , Animals , Birds/parasitology , Female , Host-Parasite Interactions , Life Cycle Stages , Male , Nova Scotia , Reproduction
15.
Radiat Res ; 147(1): 48-54, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8989369

ABSTRACT

We used a single-cell alkaline gel electrophoresis (SCAGE) assay to study repair of primarily single-stranded DNA breaks after in vitro exposure to ionizing radiation in cells from children with systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), systemic sclerosis (SSc) and dermatomyositis. Peripheral blood lymphocytes from patients with SLE, JRA and SSc had significantly greater DNA damage after irradiation with 1.5 Gy and 30 min incubation (i.e. repair time) than did those from controls, as assessed by the length of the migrating DNA comet. The mean comet tail lengths were: SLE, 42 microns; JRA, 40 microns; and SSc, 36 microns. Each of these was significantly different from controls, which had a mean comet tail length of 18 microns (P < 0.001, < 0.001 and < 0.05, respectively). Cells from patients with dermatomyositis had an average comet tail length of 22 microns and were not significantly different from controls. Understanding the etiology of the delay in DNA repair in these diseases may provide insight into disease pathogenesis.


Subject(s)
Arthritis, Juvenile/immunology , DNA Damage , DNA Repair , DNA/radiation effects , Lupus Erythematosus, Systemic/immunology , Lymphocytes/radiation effects , Adolescent , Adult , Autoimmune Diseases/immunology , Cells, Cultured , Child , Child, Preschool , Cobalt Radioisotopes , Dermatomyositis/immunology , Ethnicity , Female , Humans , Infant , Kinetics , Lymphocytes/pathology , Lymphocytes/physiology , Male , Radiation, Ionizing , Reference Values , Scleroderma, Systemic/immunology
16.
J Appl Physiol (1985) ; 81(1): 326-34, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8828681

ABSTRACT

Inhibition of DNA polymerase gamma-function mediated by 3'-azido-3'-deoxythymidine (AZT) has been proposed to cause a myopathy by reducing mitochondrial DNA (mtDNA) replication. Repeated bouts of exercise stimulate an increase in mtDNA replication, mitochondrial content, and mitochondrial volume fraction. Therefore, adaptation of rat skeletal muscle [tibialis anterior (TA)] mitochondria exposed to AZT (1 mg/ml for 35 days) and then to electrical stimulation for 8 h/day (7, 14, 21 days) with continued AZT treatment was examined. Fourteen and 21 days of stimulation increased TA cytochrome oxidase (CO) activity, mtDNA, and CO subunit III and VIc mRNA levels in both groups. The TA CO activity and CO III mRNA increases after 14 and 21 days of stimulation were diminished in AZT-treated rats. TA glyceraldehyde-3-phosphate dehydrogenase was reduced in normal rats after chronic stimulation but was unchanged in AZT-treated rats. Chronic stimulation increased the mitochondrial volume fraction by 80 and 40% in normal and AZT-treated rats, respectively. These results indicate diminution, but not complete inhibition, of mitochondrial adaptation by AZT-treated skeletal muscle in response to stimulation.


Subject(s)
Anti-HIV Agents/toxicity , Mitochondria, Muscle/physiology , Muscle, Skeletal/physiology , Zidovudine/toxicity , Animals , Blotting, Northern , Body Weight/drug effects , Citrate (si)-Synthase/metabolism , DNA Replication/drug effects , DNA, Mitochondrial/biosynthesis , DNA, Mitochondrial/drug effects , Electric Stimulation , Electron Transport Complex IV/metabolism , Male , Mitochondria, Muscle/drug effects , Mitochondria, Muscle/ultrastructure , Muscle, Skeletal/drug effects , Muscle, Skeletal/ultrastructure , RNA/biosynthesis , RNA/isolation & purification , Rats , Rats, Sprague-Dawley
17.
Am J Ophthalmol ; 123(3): 410-1, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9063259

ABSTRACT

PURPOSE: To report a case of Xanthomonas maltophilia endophthalmitis and to increase awareness of its potential as an intraocular pathogen. METHOD: Case report. RESULTS: A 76-year-old woman developed X maltophilia endophthalmitis after cataract extraction. To eradicate the infection, we performed two vitrectomies and treated the patient with numerous intravitreal antibiotic injections. CONCLUSIONS: X maltophilia is a potential intraocular pathogen in an immunocompetent host. If the infection takes a persistent course, persistent topical and intravitreal antibiotic treatment and possibly vitrectomy are needed to eradicate the infection.


Subject(s)
Cataract Extraction/adverse effects , Endophthalmitis/microbiology , Eye Infections, Bacterial/etiology , Gram-Negative Bacterial Infections/etiology , Xanthomonas , Aged , Anti-Bacterial Agents , Aqueous Humor/microbiology , Drug Therapy, Combination/therapeutic use , Endophthalmitis/drug therapy , Eye Infections, Bacterial/drug therapy , Female , Gram-Negative Bacterial Infections/drug therapy , Humans , Vitrectomy , Vitreous Body/microbiology , Xanthomonas/isolation & purification
18.
Clin Nephrol ; 12(1): 38-44, 1979 Jul.
Article in English | MEDLINE | ID: mdl-477054

ABSTRACT

Acute massive right-sided hydrothorax is a relatively rare but serious complication of peritoneal dialysis and may be responsible for the development of dyspnea during peritoneal dialysis. The pleural fluid appears to arise from the peritoneal dialyzate based on the time of its appearance and its chemical composition. It should be included in the differential diagnosis when a patient becomes dyspneic during peritoneal dialysis along with exaccerbation of congestive heart failure, pneumonia, atelectasis, and purulent bronchitis. Its occurrence is an indication to stop the peritoneal dialysis and contraindicates further use of this form of dialysis. Treatment may be conservative or aggressive (thoracentesis) depending on the clinical condition of the patient. Etiology is poorly understood. In some cases, there may be traumatic diaphragmatic fenestrations, but the majority of cases appear to be due to less well defined communications between the peritoneal and pleural spaces.


Subject(s)
Hydrothorax/etiology , Peritoneal Dialysis/adverse effects , Dyspnea/etiology , Female , Humans , Hydrothorax/diagnostic imaging , Hydrothorax/therapy , Middle Aged , Pleural Effusion/etiology , Radiography , Uremia/therapy
19.
Eur J Med Chem ; 34(7-8): 575-83, 1999.
Article in English | MEDLINE | ID: mdl-11278043

ABSTRACT

Dicationic carbazoles have been found to be highly active against a rat model of Pneumocystis carinii pneumonia (PCP). Unfortunately, amidoxime derivatives, designed as prodrugs, were inactive against PCP even though the corresponding amidines were highly active. In the present work, a series of 2,8- and 3,7-bis cationic dibenzothiophenes was synthesized and assayed for anti-PCP activity. Three of the compounds proved to be more potent and less toxic than a standard anti-PCP drug (pentamidine) when given intravenously. Unlike the carbazoles, a dibenzothiophene amidoxime prodrug given orally reduced the parasite load by more than 99%. While no quantitative correlation was seen between anti-PCP activity and DNA binding, a strong level of DNA binding was found to be necessary for antimicrobial activity.


Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/therapeutic use , Pneumonia, Pneumocystis/drug therapy , Prodrugs/chemical synthesis , Prodrugs/therapeutic use , Thiophenes/chemical synthesis , Thiophenes/therapeutic use , Animals , DNA, Fungal/drug effects , Magnetic Resonance Spectroscopy , Rats , Spectrophotometry, Infrared , Structure-Activity Relationship
20.
Biol Bull ; 201(1): 45-51, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11526062

ABSTRACT

Life-history theory predicts that parasitized hosts should alter their investment in reproduction in ways that maximize host reproductive success. I examined the timing of asexual reproduction (fragmentation and regeneration) in the polychaete annelid Pygospio elegans experimentally exposed to cercariae of the trematode Lepocreadium setiferoides. Consistent with adaptive host response, polychaetes that became infected by metacercariae of trematodes fragmented sooner than unexposed controls. Parasites were not directly associated with fission in that exposed polychaetes that did not become infected also fragmented earlier than controls. For specimens of P. elegans that were not exposed to trematodes, new fragments that contained original heads were larger than those that contained original tails, whereas original head and tail fragments did not differ in size for infected polychaetes. In infected specimens, metacercariae were equally represented in original head and tail fragments and were more likely to be found in whichever fragment was larger. Despite early reproduction, parasitism was still costly because populations of P. elegans exposed to parasites were smaller than controls when measured 8 weeks later and because exposure to cercariae reduced survivorship of newly divided polychaetes. Taken together, my results suggest that early fragmentation is a host response to minimize costs associated with parasitism.


Subject(s)
Polychaeta/physiology , Polychaeta/parasitology , Reproduction, Asexual , Trematoda/physiology , Animals
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