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1.
AJNR Am J Neuroradiol ; 43(12): E62-E63, 2022 12.
Article in English | MEDLINE | ID: mdl-36423952
2.
Pol J Microbiol ; 70(3): 401-404, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34584534

ABSTRACT

SARS-CoV-2 was found in a recovered patient's stool specimen by combining quantitative reverse transcription PCR (qRT-PCR) and genome sequencing. The patient was virus positive in stool specimens for at least an additional 15 days after he was recovered, whereas respiratory tract specimens were negative. The discovery of the complete genome of SARS-CoV-2 in the stool sample of the recovered patient demonstrates a cautionary warning that the potential mode of the virus transmission cannot be excluded through the fecal-oral route after viral clearance in the respiratory tract.


Subject(s)
COVID-19/virology , Convalescence , Feces/virology , Genome, Viral , SARS-CoV-2/genetics , Whole Genome Sequencing , Adult , COVID-19/diagnostic imaging , COVID-19/transmission , China , Cough/virology , Fever/virology , Humans , Male , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed
3.
AJNR Am J Neuroradiol ; 42(9): 1653-1660, 2021 09.
Article in English | MEDLINE | ID: mdl-34210664

ABSTRACT

BACKGROUND AND PURPOSE: Age-related macular degeneration is associated with reduced perfusion of the eye; however, the role of altered blood flow in the upstream ophthalmic or internal carotid arteries is unclear. We used ultra-high-field MR imaging to investigate whether the diameter of and blood flow in the ophthalmic artery and/or the ICA are altered in age-related macular degeneration and whether any blood flow changes are associated with disease progression. MATERIALS AND METHODS: Twenty-four patients with age-related macular degeneration and 13 similarly-aged healthy controls participated. TOF and high-resolution dynamic 2D phase-contrast MRA (0.26 × 0.26 × 2mm3, 100-ms effective sampling rate) was acquired at 7T. Vessel diameters were calculated from cross-sectional areas in phase-contrast acquisitions. Blood flow time-series were measured across the cardiac cycle. RESULTS: The ophthalmic artery vessel diameter was found to be significantly smaller in patients with age-related macular degeneration than in controls. Volumetric flow through the ophthalmic artery was significantly lower in patients with late age-related macular degeneration, with a significant trend of decreasing volumetric ophthalmic artery flow rates with increasing disease severity. The resistance index was significantly greater in patients with age-related macular degeneration than in controls in the ophthalmic artery. Flow velocity through the ophthalmic artery and ICA was significantly higher in patients with age-related macular degeneration. Ophthalmic artery blood flow as a percentage of ipsilateral ICA blood flow was nearly double in controls than in patients with age-related macular degeneration. CONCLUSIONS: These findings support the hypothesis that vascular changes upstream to the eye are associated with the severity of age-related macular degeneration. Additional investigation into the potential causality of this relationship and whether treatments that improve ocular circulation slow disease progression is warranted.


Subject(s)
Carotid Stenosis , Macular Degeneration , Magnetic Resonance Angiography , Blood Flow Velocity , Carotid Arteries , Carotid Artery, Internal/diagnostic imaging , Carotid Stenosis/diagnostic imaging , Humans , Macular Degeneration/diagnostic imaging , Ophthalmic Artery/diagnostic imaging
4.
J Food Prot ; 83(10): 1685-1692, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32421786

ABSTRACT

ABSTRACT: The U.S. Food and Drug Administration (FDA) conducted a sampling assignment in 2014 to ascertain the prevalence of Cronobacter spp. and Salmonella in the processing environment of facilities manufacturing milk powder. Cronobacter was detected in the environment of 38 (69%) of 55 facilities. The average prevalence of Cronobacter in 5,671 subsamples (i.e., swabs and sponges from different facility locations) was 4.4%. In the 38 facilities where Cronobacter was detected, the average prevalence of positive environmental subsamples was 6.25%. In 20 facilities where zone information of the sampling location was complete, Cronobacter was most frequently detected in zone 4, followed by zone 3, then zone 2, with zone 1 yielding the lowest percentage of positive samples. The prevalence of Cronobacter across the zones was statistically different (P < 0.05). There was no significant association between product type (i.e., lactose, whey products, buttermilk powder, and nonfat dried milk) and prevalence of Cronobacter in the facility. Salmonella was detected in the environment of three (5.5%) of the 55 facilities; all three facilities produced dried whey product. The overall prevalence of Salmonella in 5,714 subsamples was 0.16%. In facilities in which Salmonella was detected, the average prevalence was 2.5%. Salmonella was most frequently detected in zone 4, followed by zone 3. Salmonella was not detected in zone 1 or zone 2. The disparity between Salmonella and Cronobacter prevalence indicates that additional measures may be required to reduce or eliminate Cronobacter from the processing environment.


Subject(s)
Cronobacter sakazakii , Cronobacter , Animals , Food Microbiology , Manufacturing and Industrial Facilities , Milk , Powders , Prevalence , Salmonella , United States/epidemiology
5.
Gene Ther ; 23(1): 1-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26207935

ABSTRACT

Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer's dementia, Parkinson's disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine.


Subject(s)
Brain Ischemia/therapy , Genetic Therapy/methods , Magnetic Resonance Imaging , Neuroprotection , Animals , Brain/metabolism , Brain Ischemia/pathology , Cerebrum/pathology , DNA, Complementary/genetics , DNA, Complementary/metabolism , Dependovirus/genetics , Disease Models, Animal , Gene Expression Regulation , Genetic Vectors , Granulocyte Colony-Stimulating Factor/genetics , Granulocyte Colony-Stimulating Factor/metabolism , Humans , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Ophthalmic Solutions , PC12 Cells , Phosphorothioate Oligonucleotides/genetics , Rats
6.
J Food Prot ; 79(11): 1828-1832, 2016 11.
Article in English | MEDLINE | ID: mdl-28221903

ABSTRACT

A most-probable-number (MPN) method was used to enumerate Listeria monocytogenes in 2,320 commercial ice cream scoops manufactured on a production line that was implicated in a 2015 listeriosis outbreak in the United States. The analyzed samples were collected from seven lots produced in November 2014, December 2014, January 2015, and March 2015. L. monocytogenes was detected in 99% (2,307 of 2,320) of the tested samples (lower limit of detection, 0.03 MPN/g), 92% of which were contaminated at <20 MPN/g. The levels of L. monocytogenes in these samples had a geometric mean per lot of 0.15 to 7.1 MPN/g. The prevalence and enumeration data from an unprecedented large number of naturally contaminated ice cream products linked to a listeriosis outbreak provided a unique data set for further understanding the risk associated with L. monocytogenes contamination for highly susceptible populations.


Subject(s)
Ice Cream , Listeria monocytogenes , Disease Outbreaks , Food Contamination , Food Microbiology , Listeriosis , Prevalence , United States
8.
Diabetologia ; 53(2): 281-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19902172

ABSTRACT

AIMS/HYPOTHESIS: The majority of type 2 diabetes genome-wide association studies (GWAS) to date have been performed in European-derived populations and have identified few variants that mediate their effect through insulin resistance. The aim of this study was to evaluate two quantitative, directly assessed measures of insulin resistance, namely insulin sensitivity index (S(I)) and insulin disposition index (DI), in Hispanic-American participants using an agnostic, high-density single nucleotide polymorphism (SNP) scan, and to validate these findings in additional samples. METHODS: A two-stage GWAS was performed in Hispanic-American samples from the Insulin Resistance Atherosclerosis Family Study. In Stage 1, 317,000 SNPs were assessed using 229 DNA samples. SNPs with evidence of association with glucose homeostasis and adiposity traits were then genotyped on the entire set of Hispanic-American samples (n = 1,190). This report focuses on the glucose homeostasis traits: S(I) and DI. RESULTS: Although evidence of association did not reach genome-wide significance (p = 5 x 10(-7)), in the combined analysis SNPs had admixture-adjusted p values of p (ADD) = 0.00010-0.0020 with 8 to 41% differences in genotypic means for S(I) and DI. CONCLUSIONS/INTERPRETATION: Several candidate loci were identified that are nominally associated with S(I) and/or DI in Hispanic-American participants. Replication of these findings in independent cohorts and additional focused analysis of these loci is warranted.


Subject(s)
Atherosclerosis/genetics , Genome-Wide Association Study , Hispanic or Latino/genetics , Insulin Resistance/genetics , Polymorphism, Single Nucleotide , Adult , Chromosome Mapping/methods , DNA/genetics , Diabetes Mellitus, Type 2/genetics , Family , Fasting , Female , Genotype , Glucose/metabolism , Humans , Insulin/blood , Male , Middle Aged , Minority Groups/statistics & numerical data , Reproducibility of Results , United States , White People/genetics
9.
Diabetologia ; 52(10): 2079-86, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19641896

ABSTRACT

AIMS/HYPOTHESIS: Central obesity, insulin resistance and beta cell dysfunction are independent risk factors for incident type 2 diabetes, although few studies have used detailed measures of these disorders. Our objective was to study the association of directly measured visceral and subcutaneous adipose tissue (VAT, SAT), insulin sensitivity (S (I)) and the acute insulin response (AIR) with incident type 2 diabetes. METHODS: Participants were 1,230 Hispanic-Americans and African-Americans in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study who were free of type 2 diabetes at baseline (2000-2002). S (I) and AIR were determined from frequently sampled IVGTTs with minimal model analysis. VAT and SAT were determined by computed tomography. Impaired fasting glucose and type 2 diabetes were defined according to American Diabetes Association criteria. RESULTS: Incident type 2 diabetes was diagnosed in 90 participants after 5 years. After adjustment for age, sex, ethnicity, centre, impaired fasting glucose, triacylglycerol, HDL-cholesterol and systolic BP, both S(I) and AIR were inversely associated with type 2 diabetes (S (I), OR 0.53, 95% CI 0.39-0.73; AIR, OR 0.22, 95% CI 0.14-0.34 per SD; both p < 0.001), while both VAT and SAT were positively associated with type 2 diabetes (VAT, OR 1.68, 95% CI 1.22-2.33; SAT, OR 1.49, 95% CI 1.13-1.99; both p < 0.01). In a model including all four factors, S (I) and AIR (S (I), OR 0.55, 95% CI 0.37-0.80; AIR, OR 0.21, 95% CI 0.13-0.33; both p < 0.01) were significant predictors of type 2 diabetes, although associations with VAT and SAT were no longer significant. A significant sex x VAT interaction indicated a stronger association of VAT with type 2 diabetes in women than in men. CONCLUSIONS/INTERPRETATION: Insulin resistance, beta cell dysfunction and VAT predicted incident type 2 diabetes, with evidence of a stronger association of VAT with type 2 diabetes among women.


Subject(s)
Adiposity/physiology , Diabetes Mellitus, Type 2/epidemiology , Insulin Resistance/physiology , Insulin-Secreting Cells/pathology , Intra-Abdominal Fat/pathology , Adult , Black or African American , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/etiology , Female , Hispanic or Latino , Humans , Insulin/metabolism , Insulin/physiology , Insulin-Secreting Cells/metabolism , Male , Middle Aged , Sex Factors
10.
Hum Reprod ; 23(5): 1214-9, 2008 May.
Article in English | MEDLINE | ID: mdl-18332089

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenic, complex common genetic disease. Multiple pathways are involved in its pathogenesis, including the androgen signaling pathway and insulin signaling pathway. Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) is a putative member of the androgen receptor-chaperone-co-chaperone complex, and may play a role in androgen signaling as a co-chaperone. Polymorphisms in the SGTA gene have not been evaluated for a role in PCOS. METHODS: Women with and without PCOS (287 cases, 187 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in SGTA. SNPs and haplotypes were determined and tested for association with PCOS and component traits of PCOS. RESULTS: For SNP rs1640262, homozygotes for the minor allele were protected against PCOS (P = 0.009). Haplotype 1 (G-A-T) was associated with increased risk of PCOS (P = 0.015). In women with PCOS, haplotype 2 (A-G-C) was associated with increased insulin resistance (P = 0.013), consequently resulting in increased insulin secretion (P = 0.014). CONCLUSIONS: This study presents genetic evidence suggesting a potential role of SGTA in the pathogenesis of PCOS. SGTA may provide a connection between multiple pathways in PCOS.


Subject(s)
Carrier Proteins/genetics , Carrier Proteins/physiology , Polycystic Ovary Syndrome/genetics , Adolescent , Adult , Cohort Studies , Female , Haplotypes , Humans , Insulin Resistance/genetics , Middle Aged , Molecular Chaperones , Polymorphism, Single Nucleotide
11.
Biocontrol (Dordr) ; 51(2): 183-194, 2006 Apr.
Article in English | MEDLINE | ID: mdl-32719580

ABSTRACT

Polymerase chain reaction (PCR)-based molecular markers have been developed to detect the presence of primary parasitoids in cereal aphids and used to estimate primary parasitism rates. However, the presence of secondary parasitoids (hyperparasitoids) may lead to underestimates of primary parasitism rates based on PCR markers. This is because even though they kill the primary parasitoid, it's DNA can still be amplified, leading to an erroneous interpretation of a positive result. Another issue with secondary parasitoids is that adults are extremely difficult to identify using morphological characters. Therefore, we developed species-specific molecular markers to detect hyperparasitoids. A 16S ribosomal RNA mitochondrial gene fragment was amplified by PCR and sequenced from two secondary parasitoid species, Dendrocerus carpenteri (Curtis) (Hymenoptera: Megaspilidae) and Alloxysta xanthopsis (Ashmead) (Hymenoptera: Charipidae), four geographic isolates of the primary parasitoid, Lysiphlebus testaceipes (Cresson) (Hymenoptera: Braconidae), and six aphid species common to cereal crops. Species-specific PCR primers were designed for each insect on the basis of these 16S rRNA gene sequences. Amplification of template DNA, followed by agarose gel electrophoresis, successfully distinguished D. carpenteri and A. xanthopsis from all four isolates of L. testaceipes and all six cereal aphid species in this laboratory test.

12.
Neurology ; 60(10): 1615-20, 2003 May 27.
Article in English | MEDLINE | ID: mdl-12771251

ABSTRACT

BACKGROUND: Most clinical symptoms of Huntington disease (HD) have been attributed to striatal degeneration, but extrastriatal degeneration may play an important role in the clinical symptoms because postmortem studies demonstrate that almost all brain structures atrophy. OBJECTIVE: To fully characterize the morphometric changes that occur in vivo in HD. METHODS: High-resolution 1.5 mm T1-weighted coronal scans were acquired from 18 individuals in early to mid-stages of HD and 18 healthy age-matched controls. Cortical and subcortical gray and white matter were segmented using a semiautomated intensity contour-mapping algorithm. General linear models for correlated data of the volumes of brain regions were used to compare groups, controlling for age, education, handedness, sex, and total brain volumes. RESULTS: Subjects with HD had significant volume reductions in almost all brain structures, including total cerebrum, total white matter, cerebral cortex, caudate, putamen, globus pallidus, amygdala, hippocampus, brainstem, and cerebellum. CONCLUSIONS: Widespread degeneration occurs in early to mid-stages of HD, may explain some of the clinical heterogeneity, and may impact future clinical trials.


Subject(s)
Brain/pathology , Huntington Disease/pathology , Magnetic Resonance Imaging , Adult , Atrophy , Case-Control Studies , Female , Humans , Male , Middle Aged , Nerve Degeneration , Time Factors
13.
Eur J Neurosci ; 15(6): 991-8, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11918659

ABSTRACT

We investigated the microglial response to progressive dopamine neuron degeneration using in vivo positron emission tomography (PET) imaging and postmortem analyses in a Parkinson's disease (PD) rat model induced by unilateral (right side) intrastriatal administration of 6-hydroxydopamine (6-OHDA). Degeneration of the dopamine system was monitored by PET imaging of presynaptic dopamine transporters using a specific ligand (11)C-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane). Binding of (11)C-CFT was markedly reduced in the striatum indicating dopaminergic degeneration. Parallel PET studies of (11)C-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3 isoquinoline carboxamide) (specific ligand for activated microglia) showed increased binding in the striatum and substantia nigra indicative of a microglial response. Postmortem immunohistochemical analyses were performed with antibodies against CR3 for microglia/macrophage activation. Using a qualitative postmortem index for microglial activation we found an initially focal, then widespread microglial response at striatal and nigral levels at 4 weeks postlesion. These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging.


Subject(s)
Antigens, CD , Antigens, Neoplasm , Antigens, Surface , Avian Proteins , Blood Proteins , Dopamine/metabolism , Encephalitis/diagnostic imaging , Microglia/metabolism , Neostriatum/diagnostic imaging , Neural Pathways/diagnostic imaging , Neurons/metabolism , Substantia Nigra/diagnostic imaging , Animals , Antineoplastic Agents/pharmacology , Basigin , Carbon Radioisotopes , Encephalitis/pathology , Encephalitis/physiopathology , Gliosis/diagnostic imaging , Gliosis/pathology , Gliosis/physiopathology , Isoquinolines/pharmacology , Membrane Glycoproteins/metabolism , Microglia/pathology , Neostriatum/pathology , Neostriatum/physiopathology , Neural Pathways/pathology , Neural Pathways/physiopathology , Neurons/pathology , Oxidopamine/pharmacology , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Parkinson Disease/physiopathology , Rats , Substantia Nigra/pathology , Substantia Nigra/physiopathology , Sympatholytics/pharmacology , Tomography, Emission-Computed , Tyrosine 3-Monooxygenase/metabolism
14.
Neurology ; 57(6): 1025-8, 2001 Sep 25.
Article in English | MEDLINE | ID: mdl-11571328

ABSTRACT

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that results from the expansion of a trinucleotide (CAG) repeat on chromosome 4. Progressive degeneration of the striatum is the pathologic hallmark of the disease. Little is known about the regional selectivity of the neurodegeneration and its relationship to the genetic expansion. METHODS: The authors used high-resolution MRI to determine the relationship between the genetic expansion and the degree of striatal degeneration. Morphometric analyses of the striatum from high-resolution MR images from 27 subjects with HD were compared with those of 24 healthy control subjects. RESULTS AND CONCLUSIONS: Striatal volumes were reduced in subjects with HD as compared with control subjects, in agreement with previously published reports. Left-sided volumes were smaller than right-sided volumes in subjects with HD; in healthy subjects, right-sided volumes were smaller. Finally, volume loss was significantly correlated with CAG repeat number. These results have potential implications for the design and assessment of therapeutic agents in the future.


Subject(s)
Chromosomes, Human, Pair 4 , Corpus Striatum/pathology , Huntington Disease/genetics , Magnetic Resonance Imaging , Trinucleotide Repeats , Adult , Disease Progression , Female , Follow-Up Studies , Humans , Huntington Disease/diagnosis , Male , Middle Aged , Nerve Degeneration/genetics , Nerve Degeneration/pathology
15.
Brain Res ; 879(1-2): 204-15, 2000 Oct 06.
Article in English | MEDLINE | ID: mdl-11011024

ABSTRACT

We investigated the basal ganglia, motor cortex area 4, and supplementary motor area (SMA) using functional magnetic resonance imaging (fMRI) and five motor tasks: switching between finger and toe movements, writing, finger tapping, pronation/supination, and saccadic eye movements. We found reliable activation in the caudate nucleus and putamen in single subjects without the need for inter-subject averaging. Percent signal changes in basal ganglia were smaller by a factor of three than those in SMA or motor cortex (1% vs. 2.5-3%). There was a definite foot-dorsal, hand-ventral basal ganglia somatotopy, similar to prior data from primates. Saccadic eye movements activated the caudate nucleus significantly more than the other tasks did. Unilateral movements produced bilateral activation in the striatum even when motor cortex activation was unilateral. Surprisingly, bilateral performance of the tasks led, on average, to consistently smaller basal ganglia activation than did unilateral performance (P<0.001), suggesting less inhibition of contralateral movements during bilateral tasks. Moreover, there was a striking dominance pattern in basal ganglia motor activation: the left basal ganglia were more active than the right for right handers, regardless of the hand used. This lateralization appears much stronger than that previously reported for motor cortex. Comparisons of inter-subject and intra-subject reproducibility indicated a much larger variability in basal ganglia and SMA compared to motor cortex, in spite of similar percent signal changes in the latter two structures.


Subject(s)
Basal Ganglia/physiology , Brain Mapping/methods , Motor Activity/physiology , Motor Cortex/physiology , Psychomotor Performance/physiology , Thalamus/physiology , Adult , Female , Fingers/innervation , Functional Laterality , Hand/innervation , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Reproducibility of Results , Saccades , Toes/innervation
16.
Am J Hypertens ; 13(6 Pt 1): 704-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10912757

ABSTRACT

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.


Subject(s)
Asian People , Asian , Blood Pressure/physiology , Calmodulin-Binding Proteins/genetics , Cytoskeletal Proteins/genetics , Hypertension/genetics , Adult , Alleles , Asian/genetics , Asian People/genetics , Calmodulin-Binding Proteins/metabolism , Cytoskeletal Proteins/metabolism , DNA/analysis , DNA Primers/chemistry , Gene Frequency , Genotype , Glycine/genetics , Hawaii/ethnology , Humans , Hypertension/ethnology , Hypertension/metabolism , Hypertension/physiopathology , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , San Francisco/ethnology , Taiwan/ethnology , Tryptophan/genetics
17.
Stat Med ; 19(3): 353-67, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10649301

ABSTRACT

This paper considers the practical problem in animal carcinogenesis experiments where several treatment groups are compared with a control group in a one-way layout and the observed survival data are subject to random right-censorship. Proposed herein are multiple testing procedures based on two-sample weighted logrank statistics, each comparing an individual treatment with the control, for determining which treatments are more effective than the control. The associated p-value of claiming a certain treatment is more effective than the control is also discussed. A test-based confidence set for the scale changes between each treatment and the control is then obtained. The comparative results of a Monte Carlo error rate and power study for small sample sizes are presented. Finally, a numerical example involving renal carcinoma in mice demonstrates the feasibility of the proposed multiple testing procedures and test-based confidence set.


Subject(s)
Interleukin-12/pharmacology , Interleukin-2/pharmacology , Kidney Neoplasms/drug therapy , Models, Statistical , Animals , Confidence Intervals , Disease Models, Animal , Mice , Monte Carlo Method , Proportional Hazards Models , Survival Analysis
18.
Neuroreport ; 10(14): 2881-6, 1999 Sep 29.
Article in English | MEDLINE | ID: mdl-10549790

ABSTRACT

We demonstrate the use of magnetic resonance imaging (MRI) for detection of neurotransmitter stimulation using the dopamine transporter ligands amphetamine and CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) as pharmacological challenges. We demonstrate that the unilateral loss of a hemodynamic response to either amphetamine or CFT challenge by unilateral 6-hydroxydopamine lesioning is restored by transplantation of fetal dopamine neurons in the striatum. The time course for the hemodynamic changes parallels the time courses for dopamine release, measured by prior microdialysis studies, and also for the rotational behavior in the unilaterally lesioned animals. Transplantation of the fetal cells results in hemodynamic time courses after CFT or amphetamine challenges at the graft site that are identical to those induced both before transplantation and on the intact contralateral side. The transplantation also results in complete behavioral recovery. The spatial extent of the dopaminergic recovery in the lesioned striatum is the same when measured using either PET of tracer levels of [11C]CFT binding or MRI. These results show great promise for the application of pharmacological MRI for application to studies of dopamine cell loss and potential recovery in Parkinson's disease.


Subject(s)
Behavior, Animal/physiology , Cell Transplantation/physiology , Dopamine/physiology , Neurons/physiology , Amphetamine , Animals , Cocaine/analogs & derivatives , Dopamine Uptake Inhibitors , Female , Magnetic Resonance Imaging , Microdialysis , Rats , Rats, Sprague-Dawley , Striatonigral Degeneration , Sympathectomy, Chemical , Tomography, Emission-Computed
19.
Mov Disord ; 14(2): 326-30, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10091628

ABSTRACT

We conducted a 6-week open-label trial of riluzole (50 mg twice a day) in eight subjects with Huntington's disease. Subjects were evaluated before riluzole treatment, on treatment, and off treatment with the chorea, dystonia, and total functional capacity (TFC) scores from the Unified Huntington's Disease Rating Scale and magnetic resonance spectroscopy measurements of occipital cortex and basal ganglia lactate levels. Adverse events and safety blood and urine tests were assessed throughout the study. All subjects completed the study and riluzole was well tolerated. The age was 45+/-10.2 years (mean +/- standard deviation) and the disease duration was 6.1+/-4.1 years. The chorea rating score improved by 35% on treatment (p = 0.013) and worsened after discontinuation of treatment (p = 0.026). There were no significant treatment effects on the dystonia or TFC scores. The baseline occipital and basal ganglia lactate levels were elevated in all subjects; there was a trend toward lower lactate/creatine ratios during riluzole treatment in the basal ganglia spectra but not in occipital cortex spectra. Additional clinical studies of riluzole for both symptomatic and neuroprotective benefit in Huntington's disease are warranted.


Subject(s)
Excitatory Amino Acid Antagonists/therapeutic use , Huntington Disease/drug therapy , Neuroprotective Agents/therapeutic use , Riluzole/therapeutic use , Adult , Basal Ganglia/drug effects , Basal Ganglia/metabolism , Chorea/drug therapy , Excitatory Amino Acid Antagonists/adverse effects , Female , Humans , Huntington Disease/metabolism , Lactic Acid/metabolism , Magnetic Resonance Spectroscopy , Male , Middle Aged , Neuroprotective Agents/adverse effects , Occipital Lobe/drug effects , Occipital Lobe/metabolism , Pilot Projects , Riluzole/adverse effects , Severity of Illness Index , Single-Blind Method , Treatment Outcome
20.
Biometrics ; 55(4): 1236-40, 1999 Dec.
Article in English | MEDLINE | ID: mdl-11315075

ABSTRACT

We consider identifying the minimum effective dose (MED) in a dose-response study, where the MED is defined to be the lowest dose level producing an effect over that of the zero-dose control. Proposed herein is a nonparametric procedure based on the Mann-Whitney statistic incorporated with the step-down closed testing scheme. A numerical example demonstrates the feasibility of the proposed nonparametric procedure. Finally, the comparative results of a Monte Carlo level and power study for small sample sizes are presented and discussed.


Subject(s)
Biometry , Dose-Response Relationship, Drug , Animals , Azo Compounds/administration & dosage , Humans , Models, Statistical , Monte Carlo Method , Naphthalenesulfonates/administration & dosage , No-Observed-Adverse-Effect Level , Salmonella/drug effects , Salmonella/genetics , Toxicology/statistics & numerical data
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