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1.
Transl Psychiatry ; 14(1): 148, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38490997

ABSTRACT

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc)-a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST)-as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders-and how this relationship is mediated by alterations in the EAc-could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant-inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.


Subject(s)
Central Amygdaloid Nucleus , Humans , Animals , Female , Adolescent , Macaca mulatta , Temperament/physiology , Anxiety/metabolism , Anxiety Disorders/metabolism
2.
Cytopathology ; 28(5): 413-418, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28730704

ABSTRACT

OBJECTIVE: Persistent infection with oncogenic high risk HPV (hrHPV) types causes virtually all cases of cervical cancer. HPV 16 and 18 have been targeted for individual genotyping and vaccination because of their presence in 71% of invasive cervical cancers worldwide. Montefiore Medical Center, Bronx, New York serves a population known for ethnic and racial diversity. Given this diversity it is possible that HPV genotypes not individually detected by current testing are causing significant disease. METHODS: We conducted a retrospective analysis of liquid based cervicovaginal cytology and Cobas HPV results reported between October 5, 2015 and March 30, 2016. This included 20 483 samples from patients aged 16-95 (average age 42), with racial distribution including: African-American 32.4%, Other (includes denied, unknown, mixed, Hispanic) 52.1%, Caucasian 14.5%, Asian 0.7%, American Indian/Alaskan Native 0.3%. In all, 14 938 samples (72.9%) were submitted for clinically requested COBAS 4800 HPV testing, which separately reports HPV 16, 18 and a pool of 12 other hrHPV. RESULTS: A total of 3180 (21.5%) tested hrHPV positive. The percentage of patients with cytologic diagnosis of HSIL (high-grade squamous intraepithelial lesion) that were positive only for HPV 16 was 19.4% vs 1.8% for all cytologic diagnoses. However, only one of the HSIL cases was HPV 18 positive along with other hrHPV (OHR). Surprisingly, a majority (64.5%) was positive for only OHR. CONCLUSIONS: Further evaluation is needed to determine if this pool of other hrHPV includes individual genotypes that in our population carry a higher risk of persistence and progression to cancer.


Subject(s)
Early Detection of Cancer , Squamous Intraepithelial Lesions of the Cervix/diagnosis , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Female , Genotype , Human papillomavirus 16/genetics , Human papillomavirus 16/isolation & purification , Human papillomavirus 18/genetics , Human papillomavirus 18/isolation & purification , Humans , Mass Screening , Middle Aged , New York City/epidemiology , Papanicolaou Test , Papillomavirus Infections , Squamous Intraepithelial Lesions of the Cervix/epidemiology , Squamous Intraepithelial Lesions of the Cervix/genetics , Squamous Intraepithelial Lesions of the Cervix/virology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virology , Young Adult
3.
Lab Med ; 48(3): 207-213, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28379422

ABSTRACT

OBJECTIVE: To compare the cytologic preparations of 130 cervical specimens (from women of various ethnicities at high risk for human papillomavirus [HPV] infection) using the SurePath (SP) collection system with specimens gathered using the ThinPrep (TP) system, as processed on the Cobas 4800 analyzer, to determine which collection method more accurately identifies HPV infection. METHODS: In our prospective study, specimens were collected from 130 women of various ethnicities residing in or near Bronx County, NY. The SP-collected specimen was first processed for cytologic findings; if clinical HPV testing was requested on that specimen, it was tested using Hybrid Capture II (HC2) methodology. We tested the remnant SP-collected cell concentrate using the Cobas analyzer. Then, the TP-collected and SP-collected specimens were tested in the same run on that analyzer, and the results were compared. We also compared the results with the concurrent cytologic findings. RESULTS: The results were concordant for overall HR-HPV status in 93.8% of cases. Also, a statistically significant lower cycle threshold value was observed with Cobas testing of specimen concentrates tested via the BD SurePath Pap Test (P = .001), suggesting higher sensitivity compared with specimens tested via the ThinPrep Pap Test. CONCLUSION: Cobas 4800 HPV testing of SP-collected specimen concentrates yields comparable results to TP-collected specimen concentrates. Based on the limited data that we derived, SP collection may be a more favorable methodology than TP collection for HPV testing of individuals at high risk in our ethnically diverse, urban patient population.


Subject(s)
Cytodiagnosis/methods , Molecular Diagnostic Techniques/methods , Papillomaviridae/genetics , Papillomavirus Infections , Vaginal Smears/methods , Adolescent , Adult , Aged , Female , Humans , Middle Aged , New York City , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Polymerase Chain Reaction , Prospective Studies , Young Adult
4.
Scand J Med Sci Sports ; 27(5): 525-534, 2017 May.
Article in English | MEDLINE | ID: mdl-27292768

ABSTRACT

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined.


Subject(s)
Anterior Cruciate Ligament Injuries/prevention & control , Anterior Cruciate Ligament/physiology , Knee Joint/physiology , Physical Endurance/physiology , Adult , Athletes , Biomechanical Phenomena/physiology , Female , Humans , Risk Assessment , Risk Factors , Rotation
5.
Mol Psychiatry ; 22(5): 724-732, 2017 05.
Article in English | MEDLINE | ID: mdl-27573879

ABSTRACT

Children with an anxious temperament are prone to heightened shyness and behavioral inhibition (BI). When chronic and extreme, this anxious, inhibited phenotype is an important early-life risk factor for the development of anxiety disorders, depression and co-morbid substance abuse. Individuals with extreme anxious temperament often show persistent distress in the absence of immediate threat and this contextually inappropriate anxiety predicts future symptom development. Despite its clear clinical relevance, the neural circuitry governing the maladaptive persistence of anxiety remains unclear. Here, we used a well-established nonhuman primate model of childhood temperament and high-resolution 18fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to understand the neural systems governing persistent anxiety and to clarify their relevance to early-life phenotypic risk. We focused on BI, a core component of anxious temperament, because it affords the moment-by-moment temporal resolution needed to assess contextually appropriate and inappropriate anxiety. From a pool of 109 peri-adolescent rhesus monkeys, we formed groups characterized by high or low levels of BI, as indexed by freezing in response to an unfamiliar human intruder's profile. The high-BI group showed consistently elevated signs of anxiety and wariness across >2 years of assessments. At the time of brain imaging, 1.5 years after initial phenotyping, the high-BI group showed persistently elevated freezing during a 30-min 'recovery' period following an encounter with the intruder-more than an order of magnitude greater than the low-BI group-and this was associated with increased metabolism in the bed nucleus of the stria terminalis, a key component of the central extended amygdala. These observations provide a neurobiological framework for understanding the early phenotypic risk to develop anxiety-related psychopathology, for accelerating the development of improved interventions, and for understanding the origins of childhood temperament.


Subject(s)
Amygdala/metabolism , Anxiety Disorders/metabolism , Anxiety/metabolism , Aggression , Amygdala/diagnostic imaging , Animals , Anxiety/genetics , Anxiety Disorders/genetics , Depression/genetics , Depression/metabolism , Disease Models, Animal , Female , Inhibition, Psychological , Macaca mulatta , Neuroimaging , Phenotype , Positron-Emission Tomography , Risk Factors , Temperament/physiology
7.
Mol Psychiatry ; 19(8): 915-22, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24863147

ABSTRACT

Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.


Subject(s)
Anxiety Disorders/physiopathology , Anxiety/physiopathology , Biological Evolution , Central Amygdaloid Nucleus/physiopathology , Prefrontal Cortex/physiopathology , Animals , Brain Mapping , Child , Female , Fluorodeoxyglucose F18 , Humans , Macaca mulatta , Magnetic Resonance Imaging , Male , Neural Pathways/physiopathology , Positron-Emission Tomography
8.
Mol Psychiatry ; 18(6): 700-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23147386

ABSTRACT

The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.


Subject(s)
Anxiety , Brain/pathology , Depression , Genetic Predisposition to Disease/genetics , Receptors, Corticotropin-Releasing Hormone/genetics , Animals , Anxiety/complications , Anxiety/genetics , Anxiety/pathology , Brain/diagnostic imaging , Brain/metabolism , Depression/complications , Depression/genetics , Disease Models, Animal , Female , Fluorodeoxyglucose F18 , Genetic Association Studies , Genotype , Macaca mulatta , Male , Polymorphism, Single Nucleotide/genetics , Positron-Emission Tomography
9.
Neuroimage ; 47(4): 1230-6, 2009 Oct 01.
Article in English | MEDLINE | ID: mdl-19505582

ABSTRACT

UNLABELLED: The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology. METHODS: Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass. RESULTS: There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males. CONCLUSIONS: Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.


Subject(s)
Aniline Compounds/pharmacokinetics , Brain/diagnostic imaging , Brain/metabolism , Positron-Emission Tomography/methods , Serotonin Plasma Membrane Transport Proteins/metabolism , Sulfides/pharmacokinetics , Animals , Carbon Radioisotopes/pharmacokinetics , Female , Genotype , Humans , Macaca mulatta , Male , Protein Binding , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution
10.
Mol Psychiatry ; 13(11): 1021-7, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18414408

ABSTRACT

A variant allele in the promoter region of the serotonin transporter gene, SLC6A4, the s allele, is associated with increased vulnerability to develop anxiety-related traits and depression. Furthermore, functional magnetic resonance imaging (fMRI) studies reveal that s carriers have increased amygdala reactivity in response to aversive stimuli, which is thought to be an intermediate phenotype mediating the influences of the s allele on emotionality. We used high-resolution microPET [18F]fluoro-2-deoxy-D-glucose (FDG) scanning to assess regional brain metabolic activity in rhesus monkeys to further explore s allele-related intermediate phenotypes. Rhesus monkeys provide an excellent model to understand mechanisms underlying human anxiety, and FDG microPET allows for the assessment of brain activity associated with naturalistic environments outside the scanner. During FDG uptake, monkeys were exposed to different ethologically relevant stressful situations (relocation and threat) as well as to the less stressful familiar environment of their home cage. The s carriers displayed increased orbitofrontal cortex activity in response to both relocation and threat. However, during relocation they displayed increased amygdala reactivity and in response to threat they displayed increased reactivity of the bed nucleus of the stria terminalis. No increase in the activity of any of these regions occurred when the animals were administered FDG in their home cages. These findings demonstrate context-dependent intermediate phenotypes in s carriers that provide a framework for understanding the mechanisms underlying the vulnerabilities of s-allele carriers exposed to different types of stressors.


Subject(s)
Brain/diagnostic imaging , Brain/pathology , Serotonin Plasma Membrane Transport Proteins/genetics , Stress, Psychological/genetics , Stress, Psychological/pathology , Animals , Behavior, Animal , Brain Mapping , Disease Models, Animal , Female , Fluorodeoxyglucose F18/metabolism , Genotype , Macaca mulatta , Male , Phenotype , Polymorphism, Genetic , Positron-Emission Tomography , Stress, Psychological/diagnostic imaging , Stress, Psychological/etiology
11.
Neuroimage ; 28(3): 529-43, 2005 Nov 15.
Article in English | MEDLINE | ID: mdl-16099178

ABSTRACT

Motion correction of fMRI data is a widely used step prior to data analysis. In this study, a comparison of the motion correction tools provided by several leading fMRI analysis software packages was performed, including AFNI, AIR, BrainVoyager, FSL, and SPM2. Comparisons were performed using data from typical human studies as well as phantom data. The identical reconstruction, preprocessing, and analysis steps were used on every data set, except that motion correction was performed using various configurations from each software package. Each package was studied using default parameters, as well as parameters optimized for speed and accuracy. Forty subjects performed a Go/No-go task (an event-related design that investigates inhibitory motor response) and an N-back task (a block-design paradigm investigating working memory). The human data were analyzed by extracting a set of general linear model (GLM)-derived activation results and comparing the effect of motion correction on thresholded activation cluster size and maximum t value. In addition, a series of simulated phantom data sets were created with known activation locations, magnitudes, and realistic motion. Results from the phantom data indicate that AFNI and SPM2 yield the most accurate motion estimation parameters, while AFNI's interpolation algorithm introduces the least smoothing. AFNI is also the fastest of the packages tested. However, these advantages did not produce noticeably better activation results in motion-corrected data from typical human fMRI experiments. Although differences in performance between packages were apparent in the human data, no single software package produced dramatically better results than the others. The "accurate" parameters showed virtually no improvement in cluster t values compared to the standard parameters. While the "fast" parameters did not result in a substantial increase in speed, they did not degrade the cluster results very much either. The phantom and human data indicate that motion correction can be a valuable step in the data processing chain, yielding improvements of up to 20% in the magnitude and up to 100% in the cluster size of detected activations, but the choice of software package does not substantially affect this improvement.


Subject(s)
Brain/physiology , Image Processing, Computer-Assisted/statistics & numerical data , Magnetic Resonance Imaging/statistics & numerical data , Software , Algorithms , Artifacts , Computer Simulation , Humans , Linear Models , Memory, Short-Term/physiology , Models, Neurological , Movement , Oxygen/blood
12.
Mol Psychiatry ; 9(4): 325, 393-405, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14699431

ABSTRACT

Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia--a subtype of depression characterized by anhedonia--but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.


Subject(s)
Antidepressive Agents, Tricyclic/therapeutic use , Brain Mapping , Depressive Disorder, Major/physiopathology , Nortriptyline/therapeutic use , Prefrontal Cortex/physiopathology , Adult , Analysis of Variance , Blood Glucose/metabolism , Depressive Disorder/drug therapy , Depressive Disorder/pathology , Depressive Disorder/physiopathology , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/pathology , Electroencephalography/drug effects , Female , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Male , Middle Aged , Positron-Emission Tomography , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Reference Values
13.
Bull Entomol Res ; 92(6): 471-81, 2002 Dec.
Article in English | MEDLINE | ID: mdl-17598298

ABSTRACT

Pour-on formulations of four endectocide products were compared to assess the effect of faecal residues on insects developing in naturally-colonized dung of treated cattle. In each of three independent experiments, suppression of insects was associated with application of doramectin, eprinomectin and ivermectin, but no effect was observed for moxidectin. When data were combined across experiments to increase sample sizes, suppression of insects was observed for each compound, with the least effect being observed for moxidectin. Based on the number of species affected and duration of suppression, doramectin > ivermectin > eprinomectin >> moxidectin were ranked in descending order of adverse effect. A second set of three independent experiments was performed to assess the effect of endectocide treatment on dung degradation. Delayed degradation was observed for dung of cattle treated with doramectin, eprinomectin and moxidectin in the first experiment. No effect of treatment was detected in the second experiment. An effect of moxidectin was detected in the third experiment, but differences could not be detected with subsequent post-hoc tests. When data were combined across experiments to increase sample sizes, delayed degradation was detected only for eprinomectin. The apparent discrepancy between the low effect of moxidectin on insects versus its effect of dung degradation suggests the confounding action of other unidentified factors. Results of the current study indicate that use of moxidectin is least likely to affect the natural assemblage of insects associated with cattle dung.


Subject(s)
Feces , Insecta/drug effects , Insecticides/toxicity , Analysis of Variance , Animals , Cattle , Insecta/growth & development , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Larva/drug effects , Larva/growth & development , Macrolides/toxicity
14.
Horm Behav ; 37(4): 377-87, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10860681

ABSTRACT

Obese Zucker rats (fa/fa) are characterized by inadequate leptin signaling caused by a mutation in the leptin receptor gene. Obese Zucker females are infertile and hyporesponsive to the inductive effects of ovarian hormones on sexual behaviors. Leptin treatment reverses aspects of reproductive dysfunction due to perturbations in energy balance in other animal models. Our first experiment tested the hypothesis that intracerebroventricular (icv) leptin administration would enhance the display of sexual behaviors in obese Zucker females. A second experiment compared lean and obese Zucker females' responses to leptin, during fed and fasted conditions. Ovariectomized (OVX) Zucker rats were implanted with lateral ventricular cannulae. In Experiment 1, fasted, obese females received estradiol benzoate, progesterone, and icv injections of 3, 18, or 36 microg murine leptin or vehicle. Leptin administration reduced food intake, but did not enhance sexual behaviors. In Experiment 2, steroid-replaced, OVX lean and obese females (from a different source than those in Experiment 1) received icv injections of vehicle or 3 or 36 microg leptin under fed and fasted conditions. Leptin treatment reduced food intake and weight gain in the fed, but not the fasted, condition in both genotypes. Sexual receptivity and locomotion were not affected, but icv leptin injections reduced proceptive behaviors in ad libitum-fed rats. These data confirm previous reports that centrally administered leptin decreases food intake and weight gain in obese Zucker rats; results from Experiment 2 suggest that lean and obese females are similarly responsive to these actions of leptin. Contrary to our hypothesis, leptin treatment did not stimulate sexual behaviors; rather, the hormone appears to inhibit the display of sexual proceptivity in ad libitum-fed lean and obese Zucker female rats.


Subject(s)
Feeding Behavior/drug effects , Leptin/pharmacology , Obesity/psychology , Sexual Behavior, Animal/drug effects , Animals , Body Weight/drug effects , Eating/drug effects , Fasting/physiology , Female , Injections, Intraventricular , Leptin/administration & dosage , Motor Activity/drug effects , Obesity/genetics , Posture/physiology , Rats , Rats, Zucker , Time Factors
15.
Cancer ; 87(4): 184-9, 1999 Aug 25.
Article in English | MEDLINE | ID: mdl-10455205

ABSTRACT

BACKGROUND: The aim of this study was to quantify the prevalence of cervical smear abnormalities in sexually active adolescents and identify the effect of immune-modifying conditions. METHODS: Two hundred seventy-one females ages 13-22 years attending a clinic for sexually transmitted disease (STD) evaluation had cervical Papanicoloau (Pap) smears and completed sexual history questionnaires. Results of all follow-up Pap smears were obtained. Medical charts were available for 54 patients with cytologic follow-up and were reviewed for the presence of immune-modifying conditions. Follow-up smear results for patients with and without immune-modifying conditions were compared. Abnormality rates for all cervical smears seen in 1995 at Montefiore Medical Center were also obtained. RESULTS: The smear abnormality rate for adolescents was 20. 7% (abnormal squamous cells of undetermined significance [ASCUS], 12. 2%; low grade squamous intraepithelial lesion [LGSIL], 7.7%; high grade squamous intraepithelial lesion [HGSIL], 0.7%) compared with all adult females, for whom the rate was 13.2% (ASCUS, 9.9%; LGSIL, 2.5%; HGSIL, 0.6%; carcinoma 0.2%) (P < 0.0002). Of 20 initial ASCUS patients, 6 (30%) showed LGSIL or HGSIL on follow-up. Chart review allowed the clinical immune status of 54 patients to be determined. Of 14 patients with an immune-modifying condition (9 HIV positive patients, 3 receiving oral steroids, 1 liver transplant patient receiving steroids, and 1 with intestinal lymphangiectasia), 11 (78. 6%) developed or maintained an abnormality on cytologic follow-up. Of 40 patients with no identifiable immune-modifying condition, 11 (27.5%) developed or maintained an abnormality on cytologic follow-up (P < 0.00082). CONCLUSIONS: Sexually active adolescents are at higher risk of developing a significant cervical smear abnormality, especially LGSIL. Patients with an atypical Pap smear or immune-modifying condition require more attentive gynecologic monitoring. Cancer (Cancer Cytopathol)


Subject(s)
Immune System , Papanicolaou Test , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Neoplasms/epidemiology , Vaginal Smears , Adolescent , Adult , Disease Progression , Female , Follow-Up Studies , Humans , New York City/epidemiology , Prevalence , Risk Factors , Sexual Behavior , Sexual Partners , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/pathology
17.
J Adolesc Health ; 22(5): 389-93, 1998 May.
Article in English | MEDLINE | ID: mdl-9589340

ABSTRACT

PURPOSE: This study was undertaken to determine if homelessness could serve as a marker for previous hepatitis B infection (HBI), and thus justify prevaccination screening. METHODS: One hundred sexually active 13-21-year-olds (mean = 17 years), 74% female, attending an inner-city hospital-based adolescent clinic (HOSP), and 48 sexually active 13-21-year-olds (mean = 19 years), 40% female, attending a clinic based at an urban drop-in center (UDC) for street youth were consecutively enrolled, screened for HBI serum markers and administered a structured interview about sexual practices, sexual abuse, prior sexually transmitted diseases (STDs), and injection drug use. RESULTS: For the HOSP group, 7% were homeless and 4% were HBI positive. In the UDC group, 96% were homeless and 23% were HBI positive. Homelessness was significantly associated with HBI (p < 0.001), and this was corroborated by logistic regression analysis (p < 0.01). Other factors significantly associated with HBI in adolescents included a history of anal sex (p < or = 0.002), anal-receptive sex (p < or = 0.01), genital Chlamydia (p < or = 0.03), prostitution (p < or = 0.03), and sexual abuse (p < or = 0.002). For both populations, gender, sexual orientation, intravenous drug use, and genital sex were not related to HBI. CONCLUSION: These data indicate that homelessness and associated high-risk sexual practices may be indications for prevaccination screening for HBI in adolescents.


Subject(s)
Hepatitis B/prevention & control , Homeless Youth , Mass Screening , Risk-Taking , Adolescent , Adult , Female , Hepatitis B Vaccines , Humans , Male , Risk Factors , Sexually Transmitted Diseases , Urban Population , Vaccination
18.
J Med Entomol ; 33(3): 402-12, 1996 May.
Article in English | MEDLINE | ID: mdl-8667388

ABSTRACT

The hypothesis that ovulation in mosquitoes results in the formation of a single basal dilatation per ovariole, regardless of previous history of the ovariole, was supported for known 1- and 2-parous Culiseta inornata (Williston). The examination of histological sections of whole ovaries of Cs. inornata, before and after ovulation in the 1st gonotrophic cycle, indicated that the pedicel is destroyed during ovulation. Dissections revealed that 88% of 1- dilated ovarioles in 1-pars lacked a pedicel, and 90% of 2-pars had a mean of only 12.5 2-dilated ovarioles (10% had none). Criteria are proposed for the separation of nulliparous, 1-parous and 2-parous (anautogenous) Cs. inornata. Fifty percent of nullipars and 42% of 1-pars had a mean of 2.6 and 2.0 rogue ovarioles, respectively. The criteria account for rogue ovarioles in nullipars, but misdiagnose 2-pars as 1-pars when the former have few (or lack) diagnostic ovarioles. This diagnostic error can be reduced using structural differences in rogue versus diagnostic ovarioles.


Subject(s)
Culicidae/physiology , Animals , Culicidae/cytology , Female , Ovary/cytology , Ovary/ultrastructure , Ovulation , Reproduction
19.
J Adolesc Health ; 16(4): 324-7, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7612639

ABSTRACT

PURPOSE: To compare a combination DNA probe test which detects both N. gonorrhoeae (GC) and C. trachomatis (CT) to the current culture methodologies among a population of female adolescents at an urban teaching center. In addition, the probe test for CT was compared to a direct immunofluorescence test. METHODS: All sexually active female adolescents between the ages of 13-21 years who sought care at an urban teaching center from June 1991 through November 1991 and who required testing for sexually transmitted diseases (STDs) were recruited for this study. RESULTS: The probe test was demonstrated to be 66.6% sensitive and 94.9% specific when compared to tissue culture for CT and 50% sensitive and 98.2% specific when compared to culture for GC. We found an overall prevalence of 23.5% for CT and 3.5% for GC. CONCLUSIONS: The two rapid diagnostic tests for CT evaluated in this study demonstrated similar sensitivities. However the probe test offers advantages in that it is easier to perform, skill at reading fluorescence is not required, and one specimen yields results for both CT and GC.


Subject(s)
Chlamydia trachomatis/isolation & purification , Neisseria gonorrhoeae/isolation & purification , Adolescent , Adult , Bacteriological Techniques , Chlamydia trachomatis/growth & development , DNA Probes , Female , Humans , Neisseria gonorrhoeae/growth & development , Pilot Projects , Sensitivity and Specificity , Urban Population
20.
J Med Entomol ; 31(5): 738-46, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7966178

ABSTRACT

Rogue ovarioles were identified in laboratory-reared nulliparous and 1-parous Culex tarsalis Coquillett and in wild nulliparous C. tarsalis. Parity-diagnostic criteria were extrapolated from analysis of known nullipars and 1-pars. Diagnostic criteria were based, in part, on the number of ovarioles with no dilatation and a pedicel of greater than or equal to six adjacent cells. The high proportion of ovarioles lacking pedicels in known 1-pars and the small number of diagnostic ovarioles found in 2-pars support the findings of other researchers that ovulation destroys the pedicel and any previously formed dilatations.


Subject(s)
Culex/anatomy & histology , Animals , Culex/physiology , Entomology , Female , Manitoba , Ovulation , Parity
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