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1.
Parkinsonism Relat Disord ; 20(3): 274-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24182524

ABSTRACT

OBJECTIVE: Examine the correlates of Health Related Quality of Life (HRQL) in a large cohort of Parkinson's disease (PD) patients from National Parkinson Foundation (NPF) Centers of Excellence (COEs). BACKGROUND: Improving outcomes for PD will depend upon uncovering disease features impacting HRQL to identify targets for intervention and variables for risk-adjustment models. Differences in HRQL outcomes between COEs could uncover modifiable aspects of care delivery. METHODS: This cross-sectional study examined the relative contribution of demographic, social, clinical and treatment features potentially related to HRQL, as measured by the PDQ-39, in 4601 consecutive subjects from 18 COEs. Stepwise linear regression was utilized to identify correlates of HRQL. RESULTS: The variability in the PDQ-39 summary index score correlated with H&Y stage (R(2) = 22%), Timed up and Go (TUG) (17%), disease duration (11%), comorbidities (8%), cognitive status (8%), antidepressant use (6%) and center at which a patient received care (5%). Stepwise regression reordered the importance of the variables, with the H&Y first and TUG and the center becoming equal and the second most important variables determining the PDQ-39 total score. All independent variables together accounted for 44% of the variability in HRQL. CONCLUSIONS: We confirmed many but not all HRQL associations found in smaller studies. A novel observation was that the site of care was an important contributor to HRQL, suggesting that comparison of outcomes and processes among centers may identify best practices.


Subject(s)
Affect , Mobility Limitation , Outpatient Clinics, Hospital , Parkinson Disease/epidemiology , Parkinson Disease/psychology , Quality of Life/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Internationality , Male , Middle Aged , Outpatient Clinics, Hospital/standards , Parkinson Disease/diagnosis
2.
Environ Sci Process Impacts ; 15(3): 596-607, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23738358

ABSTRACT

The increasing use of products derived from nanotechnology has raised concern about their potential toxicity to aquatic life. This study sought to examine the comparative immunotoxicity of capped cadmium sulphide/cadmium telluride (CdS/CdTe) quantum dots (QDs) and possible impact of particle/aggregate size on two bivalves (Mytilus edulis and Elliptio complanata) and a fish (Oncorhynchus mykiss). The QDs were dispersed in sterile water and fractionated using a series of micro/ultrafiltration membranes of decreasing pore size: 450 nm, 100 nm, 50 nm, 25 nm, 100 kDa (6.8 nm), 30 kDa (4.6 nm), 10 kDa (3.2 nm) and 1 kDa (1.5 nm). The total concentrations of cadmium and tellurium were determined for the filtered material and for that retained on the filters (retentate). The immunotoxicity was determined by measuring cell viability and phagocytosis. Results revealed that nanoparticles retained on the ultrafilters had a higher Cd/Te ratio compared to the permeate fraction (ratio of 5 and 2 respectively) which could indicate that the CdS core was not associated with the permeable fraction of Cd. Our results demonstrate that the toxicity of CdS/CdTe QDs was concentration and size dependent. Large CdS/CdTe QD aggregates (25 nm < size < 100 nm) reduced phagocytosis more than did smaller nanoparticles (<25 nm). Moreover, our results revealed that the different species responded differently to these fractions. Mytilus edulis hemocytes were less sensitive to CdS/CdTe QDs than the Oncorhynchus mykiss macrophage and Elliptio complanata hemocytes.


Subject(s)
Bivalvia/drug effects , Cadmium Compounds/toxicity , Oncorhynchus mykiss/physiology , Quantum Dots , Sulfides/toxicity , Tellurium/toxicity , Animals , Bivalvia/physiology , Cadmium Compounds/chemistry , Cadmium Compounds/immunology , Cell Survival/drug effects , Hemocytes/cytology , Hemocytes/drug effects , Macrophages/cytology , Macrophages/drug effects , Particle Size , Phagocytosis/drug effects , Sulfides/chemistry , Sulfides/immunology , Tellurium/chemistry , Tellurium/immunology
3.
Parkinsonism Relat Disord ; 18(3): 268-73, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22104012

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson's disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression. METHODS: We are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events. RESULTS: 30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion. CONCLUSION: This report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long-term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD.


Subject(s)
Deep Brain Stimulation , Parkinson Disease/therapy , Patient Selection , Aged , Female , Humans , Male , Middle Aged , Pilot Projects , Single-Blind Method
4.
Prostaglandins Other Lipid Mediat ; 92(1-4): 67-72, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20381634

ABSTRACT

Loss of progesterone secretion at the end of the estrous cycle is via uterine PGF(2alpha) secretion; however, uterine PGF(2alpha) is not decreased during early pregnancy in ewes to prevent luteolysis. Instead the embryo imparts resistance to PGF(2alpha)-induced luteolysis, which is via the 2-fold increase in prostaglandins E(1) and E(2) (PGE(1), PGE(2); PGE) in the endometrium during early pregnancy. Chronic intrauterine infusion of PGE(1) or PGE(2) prevents spontaneous or an estradiol-17beta, IUD, or PGF(2alpha)-induced luteolysis. Four PGE receptor subtypes (EP(1), EP(2), EP(3), and EP(4)) and an FP receptor specific for PGF(2alpha) have been identified. The objective of this experiment was to determine the effects of EP(1), EP(2), EP(3), or FP receptor agonists in vivo on luteal mRNA for LH receptors, occupied and unoccupied LH receptors, and circulating progesterone in ewes. Ewes received a single treatment of 17-phenyl-tri-Nor-PGE(2) (EP(1), EP(3)), butaprost (EP(2)), 19-(R)-OH-PGE(2) (EP(2)), sulprostone (EP(1), EP(3)), or PGF(2alpha) (FP) receptor agonists into the interstitial tissue of the ovarian vascular pedicle adjacent to the luteal-containing ovary. 17-Phenlyl-tri-Nor-PGE(2) had no effect (P> or =0.05) on any parameter analyzed. Butaprost and 19-(R)-OH-PGE(2) increased (P< or =0.05) mRNA for LH receptors, occupied and unoccupied LH receptors, and circulating progesterone. Both sulprostone and PGF(2alpha) decreased (P< or =0.05) mRNA for LH receptors, occupied and unoccupied LH receptors, and circulating progesterone. It is concluded that both EP(3) and FP receptors may be involved in luteolysis. In addition, EP(2) receptors may mediate prevention of luteolysis via regulation of luteal mRNA for LH receptors to prevent loss of occupied and unoccupied LH receptors and therefore to sustaining luteal function.


Subject(s)
Corpus Luteum/drug effects , Corpus Luteum/physiology , Receptors, Prostaglandin E/agonists , Receptors, Prostaglandin/agonists , Sheep , Animals , Corpus Luteum/anatomy & histology , Corpus Luteum/metabolism , Estrous Cycle/drug effects , Estrous Cycle/metabolism , Female , Luteal Cells/drug effects , Luteal Cells/metabolism , Organ Size/drug effects , Pregnancy , Progesterone/blood , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, LH/genetics
5.
Prostaglandins Other Lipid Mediat ; 91(1-2): 42-50, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20060488

ABSTRACT

Loss of luteal progesterone secretion at the end of the ovine estrous cycle is via uterine PGF(2)alpha secretion. However, uterine PGF(2)alpha secretion is not decreased during early pregnancy in ewes. Instead, the embryo imparts a resistance to PGF(2)alpha. Prostaglandins E (PGE; PGE(1)+PGE(2)) are increased in endometrium and uterine venous blood during early pregnancy in ewes to prevent luteolysis. Chronic intrauterine infusion of PGE(1) or PGE(2) prevents spontaneous or IUD, estradiol-17beta, or PGF(2)alpha-induced premature luteolysis in nonbred ewes. The objective was to determine whether chronic intrauterine infusion of PGE(1) or PGE(2) affected mRNA for LH receptors, occupied and unoccupied receptors for LH in luteal and caruncular endometrium, and luteal function. Ewes received Vehicle, PGE(1), or PGE(2) every 4h from days 10 to 16 of the estrous cycle via a cathether installed in the uterine lumen ipsilateral to the luteal-containing ovary. Jugular venous blood was collected daily for analysis of progesterone and uterine venous blood was collected on day-16 for analysis of PGF(2)alpha and PGE. Corpora lutea and caruncular endometrium were collected from day-10 preluteolytic control ewes and day-16 ewes treated with Vehicle, PGE(1) or PGE(2) for analysis of the mRNA for LH receptors and occupied and unoccupied receptors for LH. Luteal weights on day-16 in ewes treated with PGE(1) or PGE(2) and day-10 control ewes were similar (P>or=0.05), but were greater (PPGE(2)>Vehicle-treated ewes. Concentrations of PGF(2)alpha and PGE in uterine venous plasma on day-16 were similar (P>or=0.05) in the three treatment groups. Luteal mRNA for LH receptors and unoccupied and occupied LH receptors were similar (P>or=0.05) in day-10 control ewes and day-16 ewes treated with PGE(2) and were lower (P

Subject(s)
Alprostadil/pharmacology , Corpus Luteum/drug effects , Endometrium/drug effects , Luteinizing Hormone/metabolism , Luteolysis/drug effects , Receptors, LH/genetics , Receptors, LH/metabolism , Alprostadil/administration & dosage , Animals , Corpus Luteum/metabolism , Corpus Luteum/physiology , Dinoprostone/administration & dosage , Dinoprostone/pharmacology , Endometrium/metabolism , Endometrium/physiology , Estrous Cycle/drug effects , Estrous Cycle/genetics , Estrous Cycle/metabolism , Female , Gene Expression Regulation/drug effects , Luteolysis/genetics , Luteolysis/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sheep , Time Factors
6.
Bratisl Lek Listy ; 110(6): 358-60, 2009.
Article in English | MEDLINE | ID: mdl-19634578

ABSTRACT

OBJECTIVE: To examine the clinical presentation of movement disorder in patients who reported a history of welding. METHODS: A retrospective chart review during a three-year period was performed on all movement disorders and patients who had been welders were identified. The clinical presentation of these patients was categorized by the movement disorder at the time of the initial neurological evaluation and by the therapy response. A comparison group was created by randomly selecting four non-welders for each welder. RESULTS: Among 1126 charts reviewed, eleven patients presented with a welder history. Parkinsonism was a common presentation in both groups: three of the eleven welders (27%) and five of the forty-one controls (12%). Dystonia was also common with 27% and 20%, respectively. Using the chi-squared analysis, the prevalence rates for both parkinsonism and dystonia were similar to controls. All of the welder patients with parkinsonism responded to dopaminomimetic therapy. Six of the eleven welders had elevated manganese levels in either blood or urine. CONCLUSIONS: Welders who present with a movement disorder such as parkinsonism or dystonia, have the prevalence rates for these disorders similar to the non-welder population (Fig. 2, Ref. 15).


Subject(s)
Manganese Poisoning/diagnosis , Movement Disorders/diagnosis , Occupational Diseases/chemically induced , Welding , Humans , Manganese Poisoning/complications , Middle Aged , Movement Disorders/etiology , Occupational Diseases/diagnosis
7.
Soc Reprod Fertil Suppl ; 64: 191-206, 2007.
Article in English | MEDLINE | ID: mdl-17491148

ABSTRACT

Experiments were conducted to further our understanding of the cellular and molecular mechanisms that regulate luteal function in ewes. Inhibition of protein kinase A (PKA) reduced (P < 0.05) secretion of progesterone from both small and large steroidogenic luteal cells. In addition, the relative phosphorylation state of steriodogenic acute regulatory protein (StAR) was more than twice as high (P < 0.05) in large vs small luteal cells. Large steroidogenic luteal cells appear to contain constitutively active PKA and increased concentrations of phosphorylated StAR which play a role in the increased basal rate of secretion of progesterone. To determine if intraluteal secretion of prostaglandin (PG) F2alpha was required for luteolysis, ewes on day 10 of the estrous cycle received intraluteal implants of a biodegradable polymer containing 0, 1 or 10 mg of indomethacin, to prevent intraluteal synthesis of PGF2alpha. On day 18, luteal weights in ewes receiving 1 mg of indomethacin were greater (P < 0.05) than controls and those receiving 10 mg were greater (P < 0.05) than either of the other two groups. Concentrations of progesterone in serum were also increased (P < 0.05) from days 13 to 16 of the estrous cycle in ewes receiving 10 mg of indomethacin. Although not required for decreased production of progesterone at the end of the cycle, intraluteal secretion of PGF2alpha appears to be required for normal luteolysis. To ascertain if oxytocin mediates the indirect effects of PGF2alpha on small luteal cells, the effects of 0, 0.1, 1 or 10 mM oxytocin on intracellular concentrations of calcium were quantified. There was a dose-dependent increase (P < 0.05) in the number of small luteal cells responding to oxytocin. Thus, oxytocin induces increased calcium levels and perhaps apoptotic cell death in small luteal cells. Concentrations of progesterone, similar to those present in corpora lutea (approximately 30 microg/g), prevented the increased intracellular concentrations of calcium (P < 0.05) stimulated by oxytocin in small cells. In large luteal cells the response to progesterone was variable. There was no consistent effect of high quantities of estradiol, testosterone or cortisol in either cell type. It was concluded that normal luteal concentrations of progesterone prevent the oxytocin and perhaps the PGF2alpha-induced increase in the number of small and large luteal cells which respond to these hormones with increased intracellular concentrations of calcium. In summary, large ovine luteal cells produce high basal levels of progesterone, at least in part, due to a constituitively active form of PKA and an enhanced phosphorylation state of StAR. During luteolysis PGF2alpha of uterine origin reduces the secretion of progesterone from the corpus luteum, but intraluteal production of PGF2alpha is required for normal luteolysis. Binding of PGF2alpha to receptors on large luteal cells stimulates the secretion of oxytocin which appears to activate PKC and may also inhibit steroidogenesis in small luteal cells. PGF2alpha also activates COX-2 in large luteal cells which leads to secretion of PGF2alpha. Once intraluteal concentrations of progesterone have decreased, oxytocin binding to its receptors on small luteal cells also results in increased levels of intracellular calcium and presumably apoptosis. Increased secretion of PGF2alpha from large luteal cells activates calcium channels which likely results in apoptotic death of this cell type.


Subject(s)
Autocrine Communication/physiology , Corpus Luteum Hormones/metabolism , Corpus Luteum/physiology , Luteolysis/metabolism , Progesterone/metabolism , Animals , Cyclic AMP-Dependent Protein Kinases/metabolism , Dinoprost/metabolism , Female , Humans , Oxytocin/metabolism , Phosphoproteins/metabolism
8.
Anim Reprod Sci ; 98(3-4): 204-24, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16616998

ABSTRACT

The objective was to compare the relative response between rams and bulls in characteristics of LH, FSH and testosterone (T) secretion, during and after long-term treatment with GnRH analogs. Animals were treated with GnRH agonist, GnRH antagonist, or vehicle (Control) for 28 days. Serial blood samples were collected on day 21 of treatment, and at several intervals after treatment. Injections of natural sequence GnRH were used to evaluate the capacity of the pituitary to release gonadotropins during and after treatment. Treatment with GnRH agonist increased basal LH and T concentrations in both rams and bulls, with a greater relative increase in bulls. Endogenous LH pulses and LH release after administration of GnRH were suppressed during treatment with GnRH agonist. Treatment with GnRH antagonist decreased mean hormone concentrations, LH and T pulse frequency, and the release of LH and T after exogenous GnRH, with greater relative effects in bulls. Rams previously treated with antagonist had a greater release of LH after administration of GnRH compared with control rams, while rams previously treated with agonist showed a reduced LH response. Bulls previously treated with agonist had reduced FSH concentrations and LH pulse amplitudes compared with control bulls while bulls previously treated with antagonist had greater T concentrations and pulse frequency. The present study was the first direct comparison between domestic species of the response in males to treatment with GnRH analogs. The findings demonstrated that differences do occur between rams and bulls in LH, FSH and testosterone secretion during and after treatment. Also, the consequences of treatment with either GnRH analog can persist for a considerable time after discontinuation of treatment.


Subject(s)
Cattle/metabolism , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/pharmacology , Gonadotropins, Pituitary/metabolism , Sheep/metabolism , Testosterone/metabolism , Animals , Dose-Response Relationship, Drug , Drug Administration Schedule , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Gonadotropins, Pituitary/blood , Luteinizing Hormone/blood , Luteinizing Hormone/metabolism , Male , Radioimmunoassay , Testosterone/blood
9.
J Neurol Sci ; 227(1): 115-8, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15546601

ABSTRACT

Previous reports have suggested that expansion of the CGG repeat located in the fragile X mental retardation 1 (FMR1) gene might be responsible for a significant number of patients with the multiple system atrophy (MSA) phenotype. Analysis of 65 MSA patients found only 4.6% displayed CGG expansions in the suspected range. This is similar to the frequency reported in the normal population, suggesting that this expansion does not play a major role in the MSA phenotype.


Subject(s)
Multiple System Atrophy/genetics , Nerve Tissue Proteins/genetics , RNA-Binding Proteins/genetics , Trinucleotide Repeat Expansion , Aged , Aged, 80 and over , Female , Fragile X Mental Retardation Protein , Humans , Male , Middle Aged , Phenotype , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction/methods , Sex Factors
10.
Biol Reprod ; 69(2): 398-403, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12672667

ABSTRACT

Our hypothesis was that luteal function, as determined by plasma progesterone concentrations, and corpus luteum (CL) size is enhanced in cattle administered an agonist of GnRH when the CL is developing as compared with administration of an agonist when the CL is fully functional. Cattle were chronically administered a GnRH agonist, azagly-nafarelin, from Day 3 to Day 21 (D3) or Day 12 to Day 21 (D12) or served as untreated control females (Day 0 = behavioral estrus). Blood samples were serially collected on Days 7 and 14 to evaluate LH secretory patterns and twice daily to measure plasma progesterone. Ultrasonographic examinations were conducted daily to record the area of the CL. CL size and plasma progesterone concentrations were both enhanced in the D3 group as compared with the control group. Progesterone was increased in the D12 group on Days 16 and 17 as compared with the control females. Treatment with GnRH agonist increased basal and mean LH concentrations in both D3 and D12 groups as compared with the controls. We rejected our hypothesis because chronic administration of a GnRH agonist increased plasma progesterone when administered both when the CL was developing and when it was fully functional. The enhanced luteal function was likely due to increased basal LH.


Subject(s)
Corpus Luteum Maintenance/drug effects , Gonadotropin-Releasing Hormone/agonists , Nafarelin/pharmacology , Animals , Behavior, Animal/drug effects , Cattle , Corpus Luteum/anatomy & histology , Corpus Luteum/diagnostic imaging , Corpus Luteum/drug effects , Estrous Cycle/physiology , Female , Luteinizing Hormone/blood , Nafarelin/analogs & derivatives , Ovulation/drug effects , Pregnancy , Progesterone/blood , Radioimmunoassay , Ultrasonography
11.
J Ocul Pharmacol Ther ; 17(4): 305-17, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11572462

ABSTRACT

The pharmacological characteristics of levobetaxolol, a single active isomer of betaxolol, were determined and compared with activities of other beta-adrenoceptor antagonists. Levobetaxolol (43-fold beta1-selective) exhibited a higher affinity at cloned human beta1 (Ki = 0.76 nM) than at beta2 (Ki = 32.6 nM) receptors, while dextrobetaxolol was much weaker at both receptors. Levobetaxolol potently antagonized functional activities at cloned human beta1 and beta2 receptors, and also at guinea pig atrial beta1, tracheal beta2 and rat colonic beta3 receptors (IC50s = 33.2 nM, 2970 nM and 709 nM, respectively). Thus, levobetaxolol was 89-times beta1-selective (vs beta2). Levobetaxolol (Ki = 16.4 nM) was more potent than dextrobetaxolol (Ki = 2.97 microM) at inhibiting isoproterenol-induced cAMP production in human non-pigmented ciliary epithelial cells. Levobunolol and (l)-timolol had high affinities at beta1 and beta2 receptors but were considerably less beta1-selective than levobetaxolol. Levo-, dextro- and racemic-betaxolol exhibited little or no affinity, except at sigma sites and Ca2+-channels (IC50s > 1 microM), at 89 other receptor/ligand binding sites. Levobetaxolol exhibited a micromolar affinity for L-type Ca2+-channels. In conscious ocular hypertensive cynomolgus monkeys, levobetaxolol was more potent than dextrobetaxolol, reducing intraocular pressure by 25.9+/-3.2% at a dose of 150 microg/eye (n = 15-30). Quantitative [3H]-levobetaxolol autoradiography revealed high levels of binding to human ciliary processes, iris, choroid/retina, and ciliary muscles. In conclusion, levobetaxolol is a potent, high affinity and beta1-selective IOP-lowering beta-adrenoceptor antagonist.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Betaxolol/pharmacology , Ciliary Body/drug effects , Intraocular Pressure/drug effects , Adrenergic beta-Agonists/pharmacology , Animals , Cell Line , Ciliary Body/cytology , Ciliary Body/metabolism , Cyclic AMP/biosynthesis , Drug Evaluation, Preclinical , Epithelial Cells/drug effects , Female , Guinea Pigs , Humans , Isomerism , Isoproterenol/antagonists & inhibitors , Isoproterenol/pharmacology , Macaca fascicularis , Male , Pigment Epithelium of Eye/drug effects , Rats , Receptors, Adrenergic, beta/metabolism
12.
Int J Eat Disord ; 30(1): 48-56, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11439408

ABSTRACT

OBJECTIVE: Body dissatisfaction and depression have consistently demonstrated a positive association in women. This study sought to determine the independence of this association from bulimic symptomatology among women diagnosed with bulimia nervosa. METHOD: Participants were 101 women who completed a controlled treatment study of bulimia nervosa and participated in follow-up assessments 10 years later. RESULTS: Findings indicated that baseline levels of depression were independent of and superior to bulimic symptoms in prospectively predicting body dissatisfaction at follow-up assessment. DISCUSSION: Findings suggest that depression may be a better prognostic indicator of body dissatisfaction than bulimic symptoms in women diagnosed with bulimia nervosa. A model in which depression represents a contributing factor for the maintenance of body dissatisfaction is discussed.


Subject(s)
Body Image , Bulimia/psychology , Depression/psychology , Adult , Bulimia/therapy , Female , Follow-Up Studies , Humans , Models, Psychological , Prognosis , Treatment Outcome
13.
Prostate ; 48(2): 79-92, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11433418

ABSTRACT

BACKGROUND: The generation of prostatic cell lines provides in vitro models for experimental studies of the pathogenesis of prostate carcinoma. Therefore, we established and characterized a new human prostate epithelial cell line, PEAZ-1 (prostate epithelial Arizona-1). METHODS: The PEAZ-1 cells were grown from a primary human prostate carcinoma specimen obtained from radical prostatectomy. The isolated cells were characterized by immunobiochemistry, immunohistochemistry, and tumorigenicity studies. RESULTS: PEAZ-1 cells are near diploid, tumorigenic, and androgen independent for cell growth. PEAZ-1 cells express N-cadherin, alpha- and beta-catenins, and p120 at cell-cell contacts, cytoplasmic laminin 5, vinculin, paxillin, and phosphotyrosine at focal adhesions, vimentin, and cytokeratins 8 and 18. They do not express plakoglobin, E-cadherin, and PSA, and do not form desmosomes and hemidesomomes. PEAZ-1 respond to ocadaic acid, a pro-apoptotic agent, by expression of p53. CONCLUSIONS: PEAZ-1 cells is a human prostate cancer cell line that has a number of mesenchymal characteristics.


Subject(s)
Prostatic Neoplasms/pathology , Tumor Cells, Cultured , Androgens/pharmacology , Cadherins/pharmacology , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Integrins/analysis , Male , Prostatectomy , Specimen Handling
14.
Hypertension ; 37(6): 1357-61, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11408377

ABSTRACT

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Disease Models, Animal , Tachycardia/etiology , Adrenergic Agents/pharmacology , Animals , Autonomic Nervous System Diseases/chemically induced , Blood Pressure/drug effects , Heart/innervation , Heart Rate , Male , Oxidopamine/pharmacology , Rats , Rats, Sprague-Dawley , Sympathectomy, Chemical , Syndrome , Tachycardia/chemically induced , Tachycardia/physiopathology , Tyramine/pharmacology
15.
J Biol Chem ; 276(28): 26099-106, 2001 Jul 13.
Article in English | MEDLINE | ID: mdl-11359780

ABSTRACT

The alpha(6) integrin is a 140-kDa (nonreduced) laminin receptor. We have identified a novel 70-kDa (nonreduced) form of the alpha(6) integrin called alpha(6)p for the latin word parvus, meaning small. The variant was immunoprecipitated from human cells using four different alpha(6)-specific monoclonal antibodies but not with alpha(3) or alpha(5) antibodies. The alpha(6)p integrin contained identical amino acid sequences within exons 13--25, corresponding to the extracellular "stalk region" and the cytoplasmic tail of the alpha(6) integrin. The light chains of alpha(6) and alpha(6)p were identical as judged by alpha(6)A-specific antibodies and electrophoretic properties. The alpha(6)p variant paired with either beta(1) or beta(4) subunits and was retained on the cell surface three times longer than alpha(6). Reverse transcription/polymerase chain reaction analysis revealed a single polymerase chain reaction product. The alpha(6)p variant was found in human prostate (DU145H, LnCaP, PC3) and colon (SW480) cancer cell lines but not in normal prostate (PrEC), breast cancer (MCF-7), or lung cancer (H69) cell lines or a variant of a prostate carcinoma cell line (PC3-N). Protein levels of alpha(6)p increased 3-fold during calcium-induced terminal differentiation in a normal mouse keratinocyte model system. A novel form of the alpha(6) integrin exists on cell surfaces that contains a dramatically altered extracellular domain.


Subject(s)
Integrins/analysis , Amino Acid Sequence , Humans , Integrins/chemistry , Integrins/genetics , Molecular Sequence Data , Organ Specificity
16.
Parkinsonism Relat Disord ; 7(3): 257-260, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11331196

ABSTRACT

There have been substantial advances in the last five years in understanding the basic and clinical pathophysiology underlying multiple system atrophy (MSA). Identification of glial cytoplasmic inclusions has been the most important organizing principle for further elucidation of underlying mechanisms. Recently, several unexpected developments at the clinical level have been reported. In this article, we will focus on two of these: (1) the recognition that substantial autonomic function is retained in MSA but not modulated appropriately, and (2) a potent pressor effect from ingestion of water, which cannot be explained by currently understood physiologic and pathophysiologic mechanisms. In some patients, water has elicited a 50% increase in blood pressure and been more therapeutically effective than any available pressor drug. By careful coordination of the pressor effect of water and the depressor effect of carbohydrate-rich food, many patients with MSA can now have their blood pressure controlled without pharmacological intervention.

18.
Prostate ; 46(3): 240-8, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11170153

ABSTRACT

BACKGROUND: The alpha6beta4 integrin and its ligand, laminin-5, are essential gene products for the maintenance and remodeling of a stratified epithelium. Apparent loss of polarized alpha6beta4 integrin and laminin-5 protein expression in invasive prostate cancer as compared to normal prostate glands is known to occur. It is unknown whether these alterations occur in prostatic intraepithelial neoplasia (PIN) lesions and whether this combined defect occurs in other epithelial cancers. METHODS: Human prostate tissues containing both normal, PIN, and cancerous regions and normal and cancer tissue from breast and colon were obtained at surgery and examined for beta4 integrin and laminin-5 using standard immunofluorescence staining methods. RESULTS: Both normal prostate glands and PIN lesions contain beta4 integrin and laminin-5. Prostate carcinoma was unique in that both beta4 integrin and laminin-5 expression was uniformly absent. In contrast, the beta4 integrin and its ligand, laminin-5 were detected in all of the colon carcinoma cases and in 60% of the breast carcinomas. CONCLUSIONS: The beta4 integrin and its ligand, laminin-5 are altered during the transition of PIN lesions to invasive prostate carcinoma. These data suggest the loss of these proteins during cancer progression. In both prostate and breast carcinoma, the normal expression pattern of the beta4 integrin and laminin-5 is interrupted, in contrast to the persistent beta4 integrin and laminin-5 expression detected in colon carcinoma.


Subject(s)
Antigens, Surface/biosynthesis , Carcinoma/metabolism , Cell Adhesion Molecules/biosynthesis , Integrins/biosynthesis , Prostatic Neoplasms/metabolism , Breast Neoplasms/metabolism , Carcinoma/pathology , Colonic Neoplasms/metabolism , Disease Progression , Humans , Integrin alpha6beta4 , Male , Microscopy, Fluorescence , Prostate/metabolism , Prostatic Intraepithelial Neoplasia/metabolism , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Neoplasms/pathology , Staining and Labeling , Kalinin
19.
J Infect Dis ; 183(1): 125-9, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11106539

ABSTRACT

Genotypes of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) from patients with KS in South Texas were examined. Open-reading frame (ORF)-K1 and ORF-K15 DNA segments from 16 KSHV isolates were amplified by polymerase chain reaction, and KSHV subtypes were assigned on the basis of sequence variations. K1 genotyping showed that 75% exhibited C subtype and 25% exhibited A subtype. K15 genotyping showed that 56% exhibited M form, of which 89% exhibited C3 K1 subtype and 44% exhibited P form. A unique isolate was found and was classified as C6 clade. All of the M KSHV isolates had been obtained from human immunodeficiency virus-negative classic KS patients >50 years of age, of whom 78% were Hispanic. Conversely, all KS patients with AIDS were <36 years of age and exhibited P form KSHV. These findings indicate that C3/M KSHV genotypes are more prevalent in South Texas (50%) than in other US regions (3%) and that M form KSHV likely existed in this region long before the AIDS epidemic.


Subject(s)
Herpesviridae Infections/virology , Herpesvirus 8, Human/genetics , Sarcoma, Kaposi/virology , Adult , Aged , Aged, 80 and over , Female , Genotype , HIV Seronegativity , HIV Seropositivity , Herpesviridae Infections/epidemiology , Herpesvirus 8, Human/classification , Humans , Male , Middle Aged , Open Reading Frames , Phylogeny , Prevalence , Texas/epidemiology
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