Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
1.
Clin Neuropsychol ; 36(1): 72-84, 2022 01.
Article in English | MEDLINE | ID: mdl-34030595

ABSTRACT

ObjectiveNeuropsychological assessment is integral to the pre-surgical deep brain stimulation (DBS) workup for patients with movement disorders. The COVID-19 pandemic quickly affected care access and shifted healthcare delivery, and neuropsychology has adapted successfully to provide tele-neuropsychological (teleNP) DBS evaluations during this time, thus permanently changing the landscape of neuropsychological practice. Method: In this paper, we discuss the lessons learned from the pandemic and we offer care management guidelines for teleNP and in-person evaluations of pre-DBS populations, with exploration of the feasibility of the different approaches for uninterrupted care access. Results: We summarize the strengths and weaknesses of these care models and we provide future directions for the state of clinical neuropsychological practice for DBS programs, with implications for broader patient populations. Conclusions: A better understanding of these dynamics will inform and educate the DBS team and community regarding the complexities of performing DBS neuropsychological evaluations during COVID-19 and beyond.


Subject(s)
COVID-19 , Deep Brain Stimulation , Telemedicine , Humans , Neuropsychological Tests , Pandemics , SARS-CoV-2
2.
Parkinsonism Relat Disord ; 86: 135-138, 2021 05.
Article in English | MEDLINE | ID: mdl-34049812

ABSTRACT

The evaluation and management of patients with movement disorders has evolved considerably due to the COVID-19 pandemic, including the assessment of candidates for deep brain stimulation (DBS) therapy. Members of the Neuropsychology Focus Group from the Parkinson Study Group Functional Neurosurgical Working Group met virtually to discuss current practices and solutions, build consensus, and to inform the DBS team and community regarding the complexities of performing DBS neuropsychological evaluations during COVID-19. It is our viewpoint that the practice of neuropsychology has adapted successfully to provide tele-neuropsychological pre-DBS evaluations during the global pandemic, thus permanently changing the landscape of neuropsychological services.


Subject(s)
COVID-19 , Deep Brain Stimulation/trends , Movement Disorders/psychology , Movement Disorders/surgery , Neuropsychological Tests , Neuropsychology/trends , Neurosurgery/trends , Pandemics , Parkinson Disease/psychology , Parkinson Disease/surgery , Deep Brain Stimulation/statistics & numerical data , Humans , Telemedicine
3.
J Dis Glob Health ; 4(1): 9-16, 2015.
Article in English | MEDLINE | ID: mdl-26247060

ABSTRACT

BACKGROUND: Increased legalization of marijuana has resulted in renewed interest in its effects on body weight and cardiometabolic risk. Conflicting data exist regarding marijuana effects on body weight, waist circumference as well as lipid profiles, blood pressure and cardiovascular disease. Furthermore, there is a dearth of data available on this effect in the black population. OBJECTIVE: To assess the metabolic profile and cardiovascular risk factors as well as body weight and waist circumference among urban black marijuana users. METHODS: A cross sectional study design involving 100 patients seen in a Family Practice clinic at University hospital of Brooklyn, NY, USA, over a period of 3 months from January 2014 to March 2014. Participants were administered a questionnaire regarding marijuana use, and other associated behaviors. Socio-demographic, laboratory, and clinical data were collected. We report measures of central tendencies, and dispersion for continuous variables and the frequency of distribution for categorical variables. RESULTS: Of the 100 patients surveyed, 57% were females. The mean (±SEM) age of the entire cohort was 46.3 years±1.5; range, 19-78 years. The mean body mass index (BMI) was 29.6 kg/m2±0.73; SBP=128.0 mmHg±1.69; DBP=76.1 mmHg±1.17. Current marijuana users had the lowest waist circumference compared to former or never users respectively (32.9±0.66 vs. 35.9±0.88 vs. 33.4±0.74), p<0.01. Diastolic blood pressure in mmHg was significantly higher among former marijuana users compared to current or never users, (80.0±2.1 vs. 73.3±2.3 vs. 73.4±1.6), p<0.01. Current marijuana users showed a tendency (not statistically significant) towards lower total cholesterol, Triglycerides (TG), High Density Lipoprotein (HDL)-cholesterol, Low Density Lipoprotein (LDL)-cholesterol, body mass index (BMI) and systolic blood pressure, compared to former users or never users. CONCLUSION: Current marijuana use is associated with significantly lower waist circumference, compared to former users and never users. Except for diastolic BP that was significantly lower among current users, other metabolic parameters showed tendency towards favorable profile. Further studies are needed to characterize the metabolic effects and to elucidate mechanisms of actions of marijuana in view of its rapid rate of utilization in the USA and around the world.

4.
Rev Stomatol Chir Maxillofac ; 113(6): 461-4, 2012 Dec.
Article in French | MEDLINE | ID: mdl-23182692

ABSTRACT

INTRODUCTION: Reconstructions of the fronto-orbital area remain a challenge to the reconstructive surgeon, due to the functional and esthetic impact. OBSERVATION: The authors present a case of a complex fronto-orbital reconstruction with a PEEK (PolyEtherEtherKetone) implant, associated with a skin expansion. DISCUSSION: With a follow-up of over three years, the cosmetic result is excellent. The authors believe that this technique is reliable, fast with long-term good results.


Subject(s)
Biocompatible Materials , Frontal Bone/surgery , Ketones , Orbit/surgery , Plastic Surgery Procedures/methods , Polyethylene Glycols , Prostheses and Implants , Skin Transplantation/methods , Tissue Expansion/methods , Aged , Benzophenones , Biocompatible Materials/chemistry , Bone Plates , Cicatrix/surgery , Dermatologic Surgical Procedures/methods , Esthetics , Follow-Up Studies , Humans , Ketones/chemistry , Male , Polyethylene Glycols/chemistry , Polymers , Titanium/chemistry , Treatment Outcome
5.
J Neurol ; 259(6): 1071-80, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22037958

ABSTRACT

Cognitive deficits in behavioral-variant frontotemporal dementia (bvFTD) and AD are linked to frontal and temporal lobe gray matter (GM) pathology. The aim of this study was to assess the relative contribution of white (WM) and GM abnormalities to cognitive dysfunction in bvFTD and AD. Fractional anisotropy (FA) for the corpus callosum, cingulum (Cg), and uncinate fasciculus (Unc) was determined in 17 bvFTD and 10 AD patients who underwent neuropsychological testing. Regressions were performed to assess the relative contribution of WM and GM abnormalities to cognitive deficits. Multiple regression analysis revealed that in bvFTD, the left anterior Cg FA was related to executive function, the right anterior Cg FA to visual-spatial attention and working memory, the right posterior Cg to visual-constructional abilities and the left Unc FA to Modified Trails Errors. After adding corresponding GM volumes, the left anterior Cg FA, the right anterior cingulate FA, the right posterior cingulate FA and the left uncinate FA remained significant predictors of the cognitive tasks. In the AD group, the left posterior Cg FA and right descending Cg FA were related to visual recall performance but did not remain significant predictors when GM volumes were added to the regression. These results suggest that reduced integrity of specific WM tracts contribute to cognitive deficits observed in bvFTD after accounting for GM atrophy. In AD, memory impairment was related to WM tract injury but this relationship was no longer observed when GM volumes were included.


Subject(s)
Cognition Disorders/pathology , Executive Function/physiology , Frontal Lobe/pathology , Frontotemporal Dementia/pathology , Nerve Fibers, Myelinated/pathology , Adult , Aged , Aged, 80 and over , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Corpus Callosum/pathology , Diffusion Tensor Imaging/methods , Female , Frontotemporal Dementia/physiopathology , Frontotemporal Dementia/psychology , Humans , Male , Middle Aged , Neuropsychological Tests
6.
Neurology ; 76(10): 870-8, 2011 Mar 08.
Article in English | MEDLINE | ID: mdl-21383323

ABSTRACT

OBJECTIVES: The globus pallidus internus (GPi) has been the primary target for deep brain stimulation (DBS) to treat severe medication-refractory dystonia. Some patients with primary cervical or segmental dystonia develop subtle bradykinesia occurring in previously nondystonic body regions during GPi DBS. Subthalamic nucleus (STN) DBS may provide an alternative target choice for treating dystonia, but has only been described in a few short reports, without blinded rating scales, statistical analysis, or detailed neuropsychological studies. METHODS: In this prospective pilot study, we analyzed the effect of bilateral STN DBS on safety, efficacy, quality of life, and neuropsychological functioning in 9 patients with medically refractory primary cervical dystonia. Severity of dystonia was scored by a blinded rater (unaware of the patient's preoperative or postoperative status) using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and 3, 6, and 12 months postsurgery. Lead location, medications, and adverse events were also measured. RESULTS: STN DBS was well-tolerated with no serious adverse effects. The TWSTRS total score improved (p < 0.001) from a mean (±SEM) of 53.1 (±2.57), to 19.6 (±5.48) at 12 months. Quality of life measures were also improved. STN DBS induced no consistent neuropsychological deficits. Several patients reported depression in the study and 3 had marked weight gain. No patients developed bradykinetic side effects from stimulation, but all patients developed transient dyskinetic movements during stimulation. CONCLUSIONS: This prospective study showed that bilateral STN DBS resulted in improvement in dystonia and suggests that STN DBS may be an alternative to GPi DBS for treating primary cervical dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that bilateral subthalamic nucleus deep brain stimulation results in significant improvement in cervical dystonia without bradykinetic side effects.


Subject(s)
Deep Brain Stimulation/methods , Subthalamic Nucleus/physiology , Torticollis/therapy , Adult , Aged , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neuropsychological Tests , Quality of Life , Statistics, Nonparametric , Torticollis/psychology , Treatment Outcome , Young Adult
7.
J Neurooncol ; 99(3): 423-31, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20853019

ABSTRACT

To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.


Subject(s)
Internet , Meningeal Neoplasms/surgery , Meningioma/surgery , Outcome Assessment, Health Care , Quality of Life , Radiosurgery , Humans
8.
Sex Dev ; 3(6): 317-25, 2009.
Article in English | MEDLINE | ID: mdl-20051675

ABSTRACT

Anti-Müllerian hormone (AMH), responsible for the regression of Müllerian ducts, is strongly expressed by eutherian fetal and postnatal Sertoli cells. Both AMH and testosterone levels are high during the period of fetal reproductive tract virilization which occurs largely in utero in eutherian mammals. Taking advantage of the fact that differentiation of the urogenital tract occurs after birth in marsupials, we studied the ontogeny and regulation of AMH in the tammar wallaby testis and related it to the expression of the androgen receptor in Sertoli cells. Testicular AMH expression was high between days 10-30 post partum, then fell to basal levels by day 60 and remained low until day 90, the oldest age examined. AMH expression was repressed by treatment of male pouch young with the potent androgen androstanediol. Thus, in the tammar, AMH expression decreases in response to androgen at the time of initial urogenital masculinization, in contrast to the situation in humans in which AMH is repressed by testosterone only at the time of puberty. The difference might be explained by the timing of androgen receptor expression which appears in tammar Sertoli cells at around day 40 of pouch life but only at a later developmental stage in eutherians.


Subject(s)
Anti-Mullerian Hormone/genetics , Down-Regulation/genetics , Macropodidae/genetics , Receptors, Androgen/metabolism , Sertoli Cells/metabolism , Urogenital System/metabolism , Virilism/genetics , Androstane-3,17-diol/pharmacology , Animals , Anti-Mullerian Hormone/metabolism , Down-Regulation/drug effects , Female , Gene Expression Regulation, Developmental/drug effects , Immunohistochemistry , In Situ Hybridization , Macropodidae/embryology , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sertoli Cells/cytology , Sertoli Cells/drug effects , Time Factors , Urogenital System/drug effects
9.
Neurology ; 68(15): 1205-12, 2007 Apr 10.
Article in English | MEDLINE | ID: mdl-17420404

ABSTRACT

BACKGROUND: The PET tracer (11)C-labeled Pittsburgh Compound-B ((11)C-PIB) specifically binds fibrillar amyloid-beta (Abeta) plaques and can be detected in Alzheimer disease (AD). We hypothesized that PET imaging with (11)C-PIB would discriminate AD from frontotemporal lobar degeneration (FTLD), a non-Abeta dementia. METHODS: Patients meeting research criteria for AD (n = 7) or FTLD (n = 12) and cognitively normal controls (n = 8) underwent PET imaging with (11)C-PIB (patients and controls) and (18)F-fluorodeoxyglucose ((18)F-FDG) (patients only). (11)C-PIB whole brain and region of interest (ROI) distribution volume ratios (DVR) were calculated using Logan graphical analysis with cerebellum as a reference region. DVR images were visually rated by a blinded investigator as positive or negative for cortical (11)C-PIB, and summed (18)F-FDG images were rated as consistent with AD or FTLD. RESULTS: All patients with AD (7/7) had positive (11)C-PIB scans by visual inspection, while 8/12 patients with FTLD and 7/8 controls had negative scans. Of the four PIB-positive patients with FTLD, two had (18)F-FDG scans that suggested AD, and two had (18)F-FDG scans suggestive of FTLD. Mean DVRs were higher in AD than in FTLD in whole brain, lateral frontal, precuneus, and lateral temporal cortex (p < 0.05), while DVRs in FTLD did not significantly differ from controls. CONCLUSIONS: PET imaging with (11)C-labeled Pittsburgh Compound-B ((11)C-PIB) helps discriminate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD). Pathologic correlation is needed to determine whether patients with PIB-positive FTLD represent false positives, comorbid FTLD/AD pathology, or AD pathology mimicking an FTLD clinical syndrome.


Subject(s)
Alzheimer Disease/diagnostic imaging , Benzothiazoles , Brain/diagnostic imaging , Dementia/diagnostic imaging , Image Enhancement/methods , Positron-Emission Tomography/methods , Aged , Aniline Compounds , Diagnosis, Differential , Humans , Male , Middle Aged , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Thiazoles
10.
Cell Death Differ ; 13(11): 1927-37, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16528385

ABSTRACT

In a model of male sterility (MTp53) owing to enforced p53 expression in spermatocytes II and spermatids of transgenic mice, we focused on the role of caspases. Most of them are expressed in all differentiation stages, but only the transcriptional levels of caspase-2 and caspase-3 are modified in MTp53 germ cells. In normal testis, cleaved caspase-3 and caspase-9 are detected during the elongation of spermatids. Despite this constitutive presence of caspases during terminal differentiation, calpains are the main effectors of germ cell loss in MTp53 testes: calpain 1 RNA levels are increased, caspase-3-like activity is markedly decreased while calpain activity is higher and the calpain inhibitor E64d ((2S, 3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester) reduces TUNEL labeling in MTp53 testis, whereas pancaspase inhibitor zVADfmk (N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone) has no effect. Our work suggests that despite the presence, and potent involvement, of caspases in male haploid cell maturation, calpains are the executioners of the death of terminally differentiating germ cells.


Subject(s)
Calpain/metabolism , Caspases/metabolism , Gene Expression , Meiosis/physiology , Spermatids/cytology , Spermatocytes/cytology , Tumor Suppressor Protein p53/metabolism , Amino Acid Sequence , Animals , Calpain/genetics , Caspase 2/chemistry , Caspase 2/genetics , Caspase 2/metabolism , Caspase 3/genetics , Caspase 3/metabolism , Caspase 9/metabolism , Cell Death , Enzyme Activation , Gene Expression Regulation, Enzymologic , Infertility, Male/metabolism , Male , Mice , Mice, Transgenic , Molecular Sequence Data , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Spermatids/metabolism , Spermatocytes/metabolism , Spermatogenesis/physiology , Testis/cytology , Tumor Suppressor Protein p53/genetics
11.
Andrologia ; 35(1): 79-83, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12558532

ABSTRACT

The foetal testis originates from a proliferation of the mesonephric and the coelomic epithelia which are colonized by the primordial germ cells. In the foetal testis, the development and functions of the three main cell type precursors (Leydig, Sertoli and germ cells) do not depend upon gonadotropins. Numerous intra- and extra-testicular factors are candidates for the control of its development and functions. To study the potential involvement of these factors, we developed an organotypic culture system. In absence of any growth factors or hormone, this system allows a development of the three main cell types which mimics that observed in vivo. The effects of different regulators (gonadotropin-releasing hormone, follicle-stimulating hormone, transforming growth factor-beta, insulin-like growth factor-I, anti-Mullerian hormone, retinoic acid, oestrogens) were tested in this system. Whether or not some of the effects observed in vitro have a physiological relevance was evaluated using appropriate transgenic mice. It is concluded that the foetal testis cannot be considered as an adult mini-testis since it has a specific physiology which largely differs from that of the immature or adult testis.


Subject(s)
Testis/embryology , Testis/growth & development , Animals , Animals, Newborn/growth & development , Cell Differentiation , Gonadotropins/physiology , Humans , Male , Organ Culture Techniques
12.
Ann Oncol ; 13(10): 1641-9, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12377655

ABSTRACT

BACKGROUND: To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: Sixty-two eligible patients with classic or prolymphocytic HCL (33 non-pretreated patients, 15 patients with relapse after previous treatment, and 14 patients with progressive disease during a treatment other than CDA) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Response status was repeatedly assessed according to the Consensus Resolution criteria. RESULTS: Complete and partial remissions were seen in 47 (76%) and 13 (21%) patients, respectively, for a response rate of 97%. All responses were achieved with a single treatment course. Most responses occurred early (i.e. within 10 weeks) after start of CDA therapy, but response quality improved during weeks and even months after treatment completion. The median time to treatment failure for all patients was 38 months. Leukopenia was the main toxicity. Granulocyte nadir (median 0.2 x 10(9)/l) was strongly associated with the incidence of infections (P = 0.0013). Non-specific lymphopenia occurred early after CDA treatment, and normal lymphocytes recovered slowly over several months. No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte subpopulation. No opportunistic infections were observed. CONCLUSIONS: One course of CDA given by subcutaneous bolus injections is very effective in HCL. The subcutaneous administration is more convenient for patients and care providers, and has a similar toxicity profile to continuous intravenous infusion. The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA.


Subject(s)
Antineoplastic Agents/pharmacology , Cladribine/pharmacology , Leukemia, Hairy Cell/drug therapy , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Cladribine/administration & dosage , Cladribine/adverse effects , Disease Progression , Female , Humans , Injections, Subcutaneous , Leukemia, Hairy Cell/pathology , Leukopenia/chemically induced , Male , Middle Aged , Recurrence , Survival
13.
Nature ; 411(6837): 546-7, 2001 May 31.
Article in English | MEDLINE | ID: mdl-11385559

ABSTRACT

The warming of the Alaskan Arctic during the past 150 years has accelerated over the last three decades and is expected to increase vegetation productivity in tundra if shrubs become more abundant; indeed, this transition may already be under way according to local plot studies and remote sensing. Here we present evidence for a widespread increase in shrub abundance over more than 320 km of Arctic landscape during the past 50 years, based on a comparison of historic and modern aerial photographs. This expansion will alter the partitioning of energy in summer and the trapping and distribution of snow in winter, as well as increasing the amount of carbon stored in a region that is believed to be a net source of carbon dioxide.


Subject(s)
Climate , Plants , Arctic Regions
14.
Neurochem Int ; 39(2): 141-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11408093

ABSTRACT

Oxidative stress may be a hallmark of several neurodegenerative disorders, including Alzheimer's disease (AD) Huntington's, and Parkinson's diseases as well as amyotrophic lateral sclerosis. Acrolein is a highly reactive product of lipid peroxidation that is elevated in the brains of persons with AD. This alkenal potentially can react with proteins by Michael addition to alter their structure and function. In the present study, we used electron paramagnetic resonance in conjunction with a protein-specific spin label to monitor synaptosomal membrane protein conformational alterations induced by acrolein. A dose-dependent increased conformational alteration was observed. Consistent with this finding, protein carbonyl levels from protein-bound acrolein were significantly elevated. However, pretreatment of synaptosomes with glutathione ethyl ester (GEE) significantly ameliorated both the conformational alterations and protein carbonyls induced by acrolein. Based on this success, we tested the hypothesis that elevated levels of endogenous glutathione (GSH) would offer protection against acrolein-induced oxidative stress. In-vivo elevation of GSH (215% over control, P<0.04) was produced by i.p. injection of N-acetylcysteine (NAC), a known precursor of GSH. Synaptosomes were treated with vehicle or 2 nM acrolein, the level of this alkenal found in AD brain. In contrast to synaptosomes from control animals, which had significantly increased protein carbonyl levels following addition of 2 nM acrolein, synaptosomes that were isolated from NAC-treated rodents and treated with 2 nM acrolein showed no increased carbonyl levels compared to untreated controls. These results demonstrate protection by increased in-vivo GSH levels against acrolein-induced oxidative stress at levels found in AD brain and are consistent with the notion that methods to increase endogenous GSH levels in neurodegenerative diseases associated with oxidative stress may be promising.


Subject(s)
Acrolein/toxicity , Brain/drug effects , Glutathione/metabolism , Lipid Peroxidation , Nerve Tissue Proteins/metabolism , Neurodegenerative Diseases/metabolism , Synaptosomes/drug effects , Acetylcysteine/administration & dosage , Animals , Brain/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Electron Spin Resonance Spectroscopy , Female , Gerbillinae , Synaptosomes/metabolism
15.
Mol Cell Endocrinol ; 172(1-2): 193-202, 2001 Feb 14.
Article in English | MEDLINE | ID: mdl-11165053

ABSTRACT

Addition of 5x10(-2) U/ml recombinant luteinizing hormone (LH) to testes from fetuses at 16.5 day post conception (dpc) cultured for 5 days increased the number of Leydig cells by 34% and the acute LH-stimulated testosterone production by 600%. To determine whether these positive effects of LH in vitro are physiologically relevant in vivo, fetuses were decapitated on days 16.5 pc (before the onset of LH expression in the hypophysis) or 18.5 pc (before the surge of LH in the fetal plasma) and removed at 21.5 dpc. The number of fetal Leydig cells per testis and the acute LH-stimulated testosterone production by the testes ex vivo were unaltered by decapitation. Since, in all groups, the number of Leydig cells doubled between 16.5 and 18.5 dpc and between 18.5 and 21.5 dpc, these results suggest that neither the appearance of new fully differentiated fetal Leydig cells nor the maintenance of differentiated functions in existing fetal Leydig cells depend on LH during late fetal life, although this hormone is present in the plasma. Decapitation reduced the testosterone concentrations in the plasma (-56%) and in the testis in vivo (-67%) and the basal testosterone secretion of the testis ex vivo (-70%). This suggests that LH is required to maintain the physiological activity of the Leydig cell during late fetal life. However, the decrease of the in vivo testosterone production after decapitation was not sufficient to impair the growth of the Wolffian ducts and the lengthening of the anogenital distance. In conclusion, during late fetal life in the rat, Leydig cells are LH-independent for their functional differentiation and LH-dependent for their activity.


Subject(s)
Cell Differentiation/drug effects , Leydig Cells/drug effects , Luteinizing Hormone/pharmacology , Animals , Cell Division/drug effects , Female , Fetus/cytology , Gestational Age , Leydig Cells/cytology , Male , Rats , Rats, Wistar , Testis/drug effects , Testis/embryology , Testis/growth & development , Testosterone/metabolism , Wolffian Ducts/drug effects , Wolffian Ducts/embryology , Wolffian Ducts/growth & development
16.
J Biol Chem ; 275(36): 27973-8, 2000 Sep 08.
Article in English | MEDLINE | ID: mdl-10854429

ABSTRACT

Anti-Müllerian hormone induces the regression of fetal Müllerian ducts and inhibits the transcription of gonadal steroidogenic enzymes. It belongs to the transforming growth factor-beta family whose members signal through a pair of serine/threonine kinase receptors and Smad effectors. Only the anti-Müllerian hormone type II receptor has been identified. Our goal was to determine whether anti-Müllerian hormone could share a type I receptor with another family member. Co-immunoprecipitation of known type I receptors with anti-Müllerian hormone type II receptor clearly showed that the bone morphogenetic protein type IB receptor was the only cloned type I receptor interacting in a ligand-dependent manner with this type II receptor. Anti-Müllerian hormone also activates the bone morphogenetic protein-specific Smad1 pathway and the XVent2 reporter gene, an anti-Müllerian hormone type II receptor-dependent effect abrogated by a dominant negative version of bone morphogenetic protein type IB receptor. Reverse amplification experiments showed that bone morphogenetic protein type IB receptor is co-expressed with anti-Müllerian hormone type II receptor in most anti-Müllerian hormone target tissues. Our data support a model in which a ligand, anti-Müllerian hormone, gains access to a shared type I receptor and Smad1 system through a highly restricted type II receptor.


Subject(s)
DNA-Binding Proteins , Glycoproteins , Growth Inhibitors/pharmacology , Protein Serine-Threonine Kinases/physiology , Proteins/metabolism , Receptors, Growth Factor/physiology , Receptors, Peptide/physiology , Testicular Hormones/pharmacology , Trans-Activators , Animals , Anti-Mullerian Hormone , Bone Morphogenetic Protein Receptors, Type I , Bone Morphogenetic Protein Receptors, Type II , CHO Cells , Cell Line , Cricetinae , Genes, Reporter , Humans , Mice , Protein Serine-Threonine Kinases/drug effects , Protein Serine-Threonine Kinases/genetics , Receptors, Cell Surface/physiology , Receptors, Growth Factor/drug effects , Receptors, Growth Factor/genetics , Receptors, Peptide/drug effects , Receptors, Peptide/genetics , Receptors, Transforming Growth Factor beta , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Smad Proteins , Smad1 Protein , Transfection , Tumor Cells, Cultured
17.
Endocrinology ; 140(5): 2084-8, 1999 May.
Article in English | MEDLINE | ID: mdl-10218958

ABSTRACT

Female transgenic mice that ectopically express high levels of human Müllerian-inhibiting substance (hMIS) under the control of the mouse metallothionein (MT) promoter lack a uterus, oviducts, and ovaries. The loss of the uterus and oviducts is consistent with the known activities for MIS. However, it is not clear if the loss of the ovaries in these transgenic females is caused by interactions of MIS with its normal receptor signaling pathway or by abnormal interactions with other transforming growth factor-beta (TGF-beta) super family receptor signaling pathways. To address this question, female mice carrying the MT-hMIS transgene that were also homozygous for a targeted deletion of the MIS type II receptor gene were generated. Although these females had high levels of circulating hMIS, they had normal reproductive tracts and ovaries with germ cells. In addition, these females were able to become pregnant and gave birth to pups. These findings demonstrate that all of the abnormalities of the reproductive system that are found in female transgenic mice that ectopically express high levels of hMIS are caused by signaling through the MIS type II receptor. These in vivo data demonstrate a high specificity for MIS and its receptor.


Subject(s)
Glycoproteins , Growth Inhibitors/physiology , Signal Transduction , Testicular Hormones/physiology , Animals , Anti-Mullerian Hormone , Fallopian Tubes/abnormalities , Female , Gene Deletion , Gene Expression , Growth Inhibitors/genetics , Homozygote , Humans , Metallothionein/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Ovary/abnormalities , Pregnancy , Promoter Regions, Genetic , Receptors, Peptide/genetics , Receptors, Peptide/physiology , Receptors, Transforming Growth Factor beta , Reproduction/genetics , Testicular Hormones/genetics , Uterus/abnormalities
18.
Biochem Biophys Res Commun ; 255(3): 580-6, 1999 Feb 24.
Article in English | MEDLINE | ID: mdl-10049753

ABSTRACT

Caveolae are plasma membrane microdomains that have been implicated in organizing and concentrating certain signaling molecules. Caveolins, constitute the main structural proteins of caveolae. Caveolae are abundant in terminally differentiated cell types. However, caveolin-1 is down-regulated in transformed cells and may have a potential tumor suppressor activity. In the lung, caveolae are present in the endothelium, smooth muscle cells, fibroblasts as well as in type I pneumocytes. The presence of caveolae and caveolin expression in the bronchial epithelium, although probable, has not been investigated in human. We were interested to see if the bronchial epithelia express caveolins and if this expression was modified in cancer cells. We thus tested for caveolin-1 and -2 expression several bronchial epithelial primary cell lines as well as eight lung cancer cell lines and one larynx tumor cell line. Both caveolin-1 and -2 are expressed in all normal bronchial cell lines. With the exception of Calu-1 cell line, all cancer cell lines showed very low or no expression of caveolin-1 while caveolin-2 expression was similar to the one observed in normal bronchial epithelial cells.


Subject(s)
Caveolins , Gene Expression Regulation, Neoplastic/genetics , Lung Neoplasms/genetics , Membrane Proteins/genetics , Caveolin 1 , Caveolin 2 , Down-Regulation/genetics , Humans , Immunohistochemistry , Membrane Proteins/metabolism , Tumor Cells, Cultured
19.
Am J Physiol ; 276(3): L501-5, 1999 03.
Article in English | MEDLINE | ID: mdl-10070115

ABSTRACT

The current study was done to look at a possible role of heat shock proteins (HSPs) in hypersensitivity pneumonitis (HP). The specific aims were to determine whether there was a difference in the expression of HSP72 in alveolar macrophages (AMs) between mice challenged with HP antigen and saline-treated control mice and between AMs obtained by bronchoalveolar lavage from 18 patients with HP and 11 normal subjects. The expression of HSP72 was studied under basal conditions and under a mild heat shock. HSP72 expression by AMs in response to in vitro stimulation with Saccharopolyspora rectivirgula was lower in AMs of control mice than in those of HP animals. HSP72 was constitutively expressed in AMs of both normal and HP subjects. Densitometric ratios showed that AMs from normal subjects responded to heat shock with a 39 degrees C-to-37 degrees C ratio of 1.72 +/- 0.18 (mean +/- SE), and AMs from HP patients responded with a ratio of 1.16 +/- 0.16 (P = 0.0377). This decreased induction by additional stress of AMs could lead to an altered immunoregulatory activity and account for the inflammation seen in HP.


Subject(s)
Heat-Shock Proteins/metabolism , Macrophages, Alveolar/metabolism , Pneumonia/etiology , Pneumonia/metabolism , Respiratory Hypersensitivity/complications , Animals , Antigens, Bacterial/immunology , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Female , HSP72 Heat-Shock Proteins , Humans , Male , Mice , Mice, Inbred C57BL , Pneumonia/pathology , Respiratory Hypersensitivity/immunology , Saccharopolyspora/immunology
20.
J Cogn Neurosci ; 10(6): 668-79, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9831736

ABSTRACT

False recognition occurs when people mistakenly claim that a novel item is familiar. After studying lists of semantically related words, healthy controls show extraordinarily high levels of false recognition to nonstudied lures that are semantic associates of study list words. In previous experiments, we found that both Korsakoff and non-Korsakoff amnesic patients show reduced levels of false recognition to semantic associates, implying that the medial temporal/diencephalic structures that are damaged in amnesic patients are involved in the encoding and/or retrieval of information that underlies false recognition. These data contrast with earlier results indicating greater false recognition in Korsakoff amnesics than in control subjects. The present experiment tests the hypothesis that greater or lesser false recognition of semantic associates in amnesic patients, relative to normal controls, can be demonstrated by creating conditions that are more or less conducive to allowing true recognition to suppress false recognition. With repeated presentation and testing of lists of semantic associates, control subjects and both Korsakoff and non-Korsakoff amnesics showed increasing levels of true recognition across trials. However, control subjects exhibited decreasing levels of false recognition across trials, whereas Korsakoff amnesic patients showed increases across trials and non-Korsakoff amnesics showed a fluctuating pattern. Consideration of signal detection analyses and differences between the two types of amnesic patients provides insight into how mechanisms of veridical episodic memory can be used to suppress false recognition.


Subject(s)
Amnesia/physiopathology , Memory/physiology , Aged , Alcohol Amnestic Disorder/complications , Alcohol Amnestic Disorder/physiopathology , Alcoholism/complications , Alcoholism/physiopathology , Amnesia/etiology , Female , Humans , Male , Middle Aged , Verbal Learning
SELECTION OF CITATIONS
SEARCH DETAIL
...