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3.
J Fr Ophtalmol ; 44(6): 855-862, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34020811

ABSTRACT

PURPOSE: To compare two distinct surgical techniques in the management of chronic Primary Lacrimal Canaliculitis (PLC) with clinically detectable concretions. MATERIALS AND METHODS: Inclusion criteria: Patients presenting with symptoms consistent with the diagnosis of primary lacrimal canaliculitis (PLC) with ocular involvement were gathered. Gomori-Grocott Methenamine Silver test was used for concretion staining. Two groups were identified based on the surgical technique. Group A consisted of patients who underwent a punctum sparing canalicular curettage using a chalazion curette, while the patients in Group B underwent one-snip punctoplasty with lateral canaliculotomy. Failure was defined as recurrence of the initial symptoms at any time (ocular and canalicular inflammation with purulent discharge and pouting punctum). The results were analyzed by comparisons using a Fisher's exact test. RESULTS: Ninety-six consecutive patients (96) with a confirmed diagnosis of PLC underwent surgical treatment between 1987 and 2017. Data were collected and divided based on the surgical technique discussed above (Group A and B). Group A: 51 cases with a mean follow-up time of 22 months [1-224] presented with a mean age of 51.5 [25-83] and a surgical failure rate of 19.6%. Group B: 45 patients with a mean follow-up time of 27 months [1-176], a mean age of 68 [17-87] years and a surgical failure rate of 4.4%. Statistical significance was demonstrated, with a p-value of 0.033, odds ratio (OR) of 0.1936 and Standard Deviation (SD) at a 95% confidence interval of [0.0195-0.9885]. CONCLUSIONS: One-snip punctoplasty with lateral canaliculotomy is a simple, fast and effective procedure that allows better anatomical visualization intraoperatively and is thus shown to be statistically superior to punctum sparing canalicular curettage using a chalazion curette.


Subject(s)
Canaliculitis , Lacrimal Apparatus , Adolescent , Adult , Aged , Aged, 80 and over , Canaliculitis/surgery , Chronic Disease , Curettage , Eye , Humans , Middle Aged , Neoplasm Recurrence, Local , Young Adult
4.
Curr Oncol ; 27(3): e246-e250, 2020 06.
Article in English | MEDLINE | ID: mdl-32669929

ABSTRACT

Background: Chemotherapy-induced T cell dysfunction, resulting from treatment of multiple myeloma (mm), enhances the risk for reactivation of latent tuberculous infection (ltbi). However, routine screening for ltbi has its limitations. The objective of the present study was to assess the number of patients treated for ltbi both before and after the introduction of a consistent tuberculin skin test (tst) screening program for patients with mm at our cancer centre. Methods: This retrospective observational study analyzed adult patients with mm treated with autologous hematopoietic stem-cell transplantation from 1 January 2013 to 31 December 2014, for whom tst was consistently performed at our cancer facility. Baseline demographic characteristics of patients who received tst testing and ltbi therapy were compared with those of a pre-intervention cohort of patients (1 January 2008 to 31 December 2009) who were not tested. Results: During the post-intervention period, 170 patients with mm had a tst. In 14 patients (8.2%) results were positive, and 11 of the 14 received ltbi therapy. Of another 12 patients with radiographic imaging changes consistent with prior granulomatous disease and negative tst results, 2 were treated. No cases of tuberculosis (tb) reactivation were noted in individuals who completed ltbi therapy. One case of active tb was diagnosed in a patient with a negative tst. In contrast, in the pre-intervention matched cohort of 170 patients, no tsts were performed, and no cases of active tb were documented. Conclusions: Patients with mm could benefit from a consistent tst testing policy coupled with subsequent ltbi therapy. However, universal testing might not be required. A targeted program combining evaluation of host risk factors, imaging findings, and screening tests might optimize ltbi diagnosis and management, and thus be effective in preventing the development of active tb in at-risk patients with mm.


Subject(s)
Cancer Care Facilities/standards , Latent Tuberculosis/diagnosis , Latent Tuberculosis/prevention & control , Mass Screening/methods , Multiple Myeloma/complications , Tuberculin Test/methods , Canada , Early Detection of Cancer , Female , Humans , Male , Middle Aged , Multiple Myeloma/pathology , Retrospective Studies
6.
Auton Neurosci ; 210: 34-43, 2018 03.
Article in English | MEDLINE | ID: mdl-29246398

ABSTRACT

In peripheral tissues, aldosterone alters expression of multiple genes, including the clock gene Period 1 (Per1), 11 beta-hydroxysteroid dehydrogenase-2 (11-HSD2), and α-ENAC, the epithelial sodium channel subunit. We evaluated the impact of chronic aldosterone exposure (DOCA) and salt intake on nocturnal changes in gene expression in the male Sprague Dawley rat brain. Additionally, genes associated with the orexin (ORX) system were also evaluated based on the role of this neuropeptide in arousal, feeding and hypertension and an interconnection with Per1 expression. DOCA/salt treatment increased saline intake primarily at night, elevated arterial pressure and lowered heart rate. In the medulla oblongata, DOCA/salt upregulated Per1, 11-HSD2, and α-ENAC expression independent of time of day, but did not change ORX receptor type 1 (ORX-R1) or type 2 (ORX-R2) expression. ORX-R1, and ORX-R2 expression in the medulla did however correlate with Per1 expression following DOCA/salt treatment but not in controls. In the hypothalamus, DOCA/salt treatment upregulated Per1, ORX-A, and ORX-R2 expression, in general, and Per1 and ORX-A expression at night. ORX-A, ORX-R1 and ORX-R2 expression in the hypothalamus correlated with Per1 expression following DOCA/salt but not in controls. These findings demonstrate for the first time that DOCA/salt hypertension modulates ORX gene expression in the brain and suggest that changes in expression in the ORX system may occur directly or indirectly via aldosterone-induced changes in Per1 expression. Our findings also build on emerging evidence that monitoring gene expression during both the day and night is critical to understanding the role of specific genes in hypertension.


Subject(s)
Desoxycorticosterone/pharmacology , Hypertension/pathology , Hypothalamus/drug effects , Medulla Oblongata/drug effects , Orexins/metabolism , Period Circadian Proteins/metabolism , Up-Regulation/drug effects , Analysis of Variance , Animals , Blood Pressure/drug effects , Circadian Rhythm/physiology , Disease Models, Animal , Heart Rate/drug effects , Hypertension/chemically induced , Hypothalamus/metabolism , Male , Medulla Oblongata/metabolism , Orexin Receptors/genetics , Orexin Receptors/metabolism , Orexins/genetics , Period Circadian Proteins/genetics , Rats , Rats, Sprague-Dawley , Sodium Chloride/pharmacology
8.
Neurogastroenterol Motil ; 26(9): 1323-32, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25070610

ABSTRACT

BACKGROUND: Functional gastrointestinal disorders (FGID) patients report poor health-related quality of life (HRQOL) and experience high rates of psychiatric and extraintestinal functional disorder (EIFD) comorbidity. The independent influence of these comorbidities on HRQOL and symptom burden remains unknown. We sought to determine whether FGID with mood or EIFD comorbidity have poorer HRQOL and greater GI symptom burdens; to determine the influence of comorbidities on HRQOL in FGID independent of bowel symptoms. METHODS: Subjects reported on comorbidities (anxiety, depression, somatization, EIFD), FGID criteria (irritable bowel syndrome, IBS; functional dyspepsia, FD) using ROME III Research questionnaire, GI symptom burden, and HRQOL. Differences in measures were assessed between subjects with and without ROME III criteria. Multiple regression determined the relative contribution of comorbidities to HRQOL, and mediation analysis explored whether comorbidity influences HRQOL. KEY RESULTS: In a cohort of 912 GI outpatients (47.2 ± 1.5 years, 75.8% female), 606 (66.4%) met Rome III IBS and/or FD criteria. Comorbidities were common in FGID (≥1 in 77.4%), leading to lower HRQOL and greater GI symptom burden (each p < 0.05). Poorer HRQOL was predicted by both psychiatric and EIFD comorbidity (each p < 0.05) independent of GI symptoms (p < 0.001). Comorbidities together exerted a greater effect on predicted variation in HRQOL (70.9%) relative to GI symptoms (26.5%). CONCLUSIONS & INFERENCES: Psychiatric and EIFD comorbidities are common in FGID, decrease HRQOL and are associated with greater GI symptom burdens; these factors were stronger predictors of HRQOL than GI symptoms in FGID patients.


Subject(s)
Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Mental Disorders/epidemiology , Quality of Life , Adult , Anxiety/epidemiology , Comorbidity , Depression/epidemiology , Female , Gastrointestinal Diseases/psychology , Humans , Irritable Bowel Syndrome/physiopathology , Irritable Bowel Syndrome/psychology , Male , Middle Aged , Severity of Illness Index , Somatoform Disorders/epidemiology
9.
Pol J Pathol ; 64(4): 319-21, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24375050

ABSTRACT

We present a case of a 75-year-old female with a subcutaneous back mass diagnosed as myoepithelioma of soft tissue. The diagnosis of this tumor may be challenging and familiarity with its broad morphological spectrum is important to distinguish it from a number of histologically similar soft tissue proliferations, in particular those displaying a prominent myxoid stroma. The correct diagnosis can be facilitated by the use of a panel of confirmatory immunohistochemical markers, including cytokeratins, neural, and muscular antigens, revealing the myoepithelial nature of the tumor cells.


Subject(s)
Biomarkers, Tumor/metabolism , Myoepithelioma/diagnosis , Soft Tissue Neoplasms/diagnosis , Aged , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Myoepithelioma/metabolism , Myoepithelioma/pathology , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/pathology
10.
J Environ Sci Health B ; 46(8): 655-61, 2011.
Article in English | MEDLINE | ID: mdl-21806461

ABSTRACT

Soil fumigation to control pests and pathogens is an important part of current agricultural practice. A reduction in fumigant emissions is required to ensure worker safety and environment health. A field trial in Florida was conducted to investigate whether carbonating Telone C35™ ((Z)- and (E)-1,3-dichloropropene with 35 % chloropicrin) would improve the delivery of the fumigant to such an extent that the application rate could be decreased without sacrificing efficacy. All treatments were carried out in three replications in a complete block design. The use of carbon dioxide (CO(2)) to carbonate and pressurize Telone C35 provided quicker and deeper distribution initially compared to application by nitrogen gas (N(2)) pressurization. The deeper distribution of Telone C35 components found with CO(2) application may have lowered the initial concentration of Telone C35, but it did not appreciably alter the disappearance rate of the three chemicals, chloropicrin, (Z)- and (E)-1,3-dichloropropene. The faster vertical distribution within the bedded soil of the Telone C35 by CO(2) did enhance volatilization of the active ingredients into the atmosphere compared to volatilization of similar reduced rate applied by N(2) pressurization. However, the cumulative amount volatilized from the carbonated fumigant beds at 75 % application rate was lower than the cumulative amount emitted by full rate of Telone C35 using N(2). The efficacy of the carbonated Telone C35 at a lower application rate was statistically equivalent to that of non-carbonated fumigant using N(2) pressurized injection at a higher application rate, based on weed enumeration and the root-knot nematode galling index.


Subject(s)
Allyl Compounds/chemistry , Fumigation/methods , Pesticides/pharmacology , Soil/analysis , Animals , Carbon Dioxide/chemistry , Carbonates/chemistry , Hydrocarbons, Chlorinated , Nematoda/drug effects , Pesticides/chemistry , Soil/parasitology , Volatilization
11.
Comput Biol Med ; 36(7-8): 817-36, 2006.
Article in English | MEDLINE | ID: mdl-16139263

ABSTRACT

Modern medical information management is a knowledge intensive activity requiring a high degree of interoperability across various health management entities. Ontology-based multi-agent systems provide a framework for interactions in a distributed medical systems environment without the limitations of a more traditional client server approach. In this paper, we describe electronic Medical Agent System (eMAGS) a multi-agent system with an ontology based on an accepted public health message standard, Health Level Seven (HL7), to facilitate the flow of patient information across a whole healthcare organisation.


Subject(s)
Medical Informatics Applications , Computer Communication Networks , Humans , Information Systems , Integrated Advanced Information Management Systems , Medical Records Systems, Computerized
12.
J Nematol ; 37(4): 483-8, 2005 Dec.
Article in English | MEDLINE | ID: mdl-19262895

ABSTRACT

This study examined the effects of three application methods (chisel injection, Avenger coulter injection, and drip irrigation) and two plastic films (polyethylene film [PE] and virtually impermeable film [VIF]) on distribution of cis- and trans- 1,3-dichloropropene (1,3-D) and chloropicrin (CP) in a Florida sandy soil after application of Telone C35 or Telone In-Line. Regardless of application method, VIF retained greater amounts of cis- and trans-1,3-D and CP in the root zone with longer residential time than PE. There was better retention of the three compounds in the root zone when applied with the Avenger coulter injection rig than chisel injection, especially in combination with VIF. Distribution of the three compounds in the root zone was less predictable when applied by drip irrigation. Following drip irrigation, more than 50% of the three compounds in the PE and VIF-covered beds was found near the end of the drip tapes in one experiment, whereas the distribution was much more uniform in the root zone in a second experiment. Among the three biologically active compounds, CP disappeared from the root zone more rapidly than cis- and trans-1,3-D, especially in the PE-covered beds.

13.
J Environ Sci Health B ; 39(4): 505-16, 2004 May.
Article in English | MEDLINE | ID: mdl-15473633

ABSTRACT

With the phase-out of methyl bromide scheduled for 2005, alternative fumigants are being sought. This study of Telone C35, a mixture of (Z)- and (E)-1,3-dichloropropene (1,3-D) with chloropicirin (CP), focuses on its emissions, distribution, and persistence in Florida sandy soil in microplots with different soil-water and organic matter carbon (C) content with and without two different plastic film mulches. The addition of CP did not affect the physical behavior of the isomers of 1,3-D. Slower subsurface dispersion and longer residence time of the mixed fumigant occurred at higher water content. An increase in the percent organic carbon in the soil led to a more rapid decrease for chloropicirin than for 1,3-dichloropene isomers. The use of a virtually impermeable film (VIF) for soil cover provided a more even distribution and longer persistence under all the conditions studied in comparison to polyethylene (PE) film cover or no cover. The conditions of near field capacity water content, low organic matter, and a virtually impermeable film cover yielded optimum conditions for the distribution, emission control, and persistence of Telone C35 in a Florida sandy soil.


Subject(s)
Allyl Compounds/analysis , Chemical Warfare Agents/analysis , Hydrocarbons, Chlorinated/analysis , Soil Pollutants/analysis , Fumigation , Organic Chemicals , Permeability , Plastics , Silicon Dioxide , Soil , Water
14.
J Pharm Pharmacol ; 55(12): 1701-6, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14738599

ABSTRACT

There is a renewed interest in thalidomide for use in malignancies and systemic inflammatory diseases. Reduced renal function is not uncommon among patients with these disease states but the pharmacokinetics has not been fully investigated. The aim of this study was to investigate the pharmacokinetics of thalidomide in haemodialysis patients while on and off dialysis and in myeloma patients with varying degrees of renal function. Two studies were performed. To establish the pharmacokinetics of thalidomide in patients with mild to moderate renal failure, blood samples were taken over 12 weeks from 40 patients with multiple myeloma. A second study was performed in six patients with end-stage renal disease both on a non-dialysis day and before and during a haemodialysis session. Thalidomide concentration was determined by HPLC. A one-compartment open model with first-order absorption and elimination was used to fit total thalidomide concentration to population pharmacokinetics and statistical models using the NONMEM program. Clearance and volumes were slightly below 10 L h-1 and 1 L kg-1, respectively, in both patient groups. The inter- and intra-patient variability was low. Clearance was doubled during dialysis. There was no correlation between thalidomide clearance and renal function. In conclusion, the pharmacokinetics of thalidomide in patients with renal failure are very similar to values reported by others for patients with normal renal function. Although clearance during dialysis is doubled, thalidomide dose need not be changed for patients with decreased kidney function. There is also no need for a supplementary dose due to haemodialysis.


Subject(s)
Immunosuppressive Agents/pharmacokinetics , Kidney Failure, Chronic/metabolism , Multiple Myeloma/metabolism , Renal Dialysis , Thalidomide/pharmacokinetics , Adult , Aged , Confidence Intervals , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged
15.
J Fam Pract ; 50(6): 513-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11401737

ABSTRACT

OBJECTIVE: The researchers wanted to determine the weight management experiences of patients in primary care, and what those patients want from their physicians. STUDY DESIGN: Patients completed a survey in a primary care waiting room. Afterward they were measured for body mass index (BMI). POPULATION: A total of 410 consecutive adult patients in 2 primary care practices at the University of California, San Francisco, were approached, and 366 (89%) completed the survey. OUTCOMES MEASURED: The primary outcomes were patient attitudes about weight loss, previous weight management experiences with their current physicians, and future preferences for weight management within the primary care relationship. RESULTS: Ninety-seven percent of the obese patients (BMI > 30), 84% of the overweight patients (BMI=25-30), and 39% of the non-overweight patients (BMI < 25) thought they needed to lose weight. Forty-nine percent of the obese patients, 24% of the overweight patients, and 12% of the non-overweight patients had discussed weight with their current physicians. The types of weight management assistance that patients most wanted from their physicians were: (1) dietary advice, (2) help with setting realistic weight goals, and (3) exercise recommendations. CONCLUSIONS: Although most patients believe they should lose weight, this is often not discussed during office visits. Most patients (especially those who are overweight or obese) want more help with weight management than they are getting from their primary care physicians.


Subject(s)
Attitude to Health , Family Practice/methods , Obesity/prevention & control , Obesity/psychology , Primary Health Care/methods , Adult , Aged , Body Mass Index , Communication , Diet, Reducing , Exercise Therapy , Female , Humans , Male , Middle Aged , Needs Assessment , Nutritional Sciences/education , Obesity/diagnosis , Office Visits , Patient Education as Topic , Patient Participation , Physician-Patient Relations , San Francisco , Surveys and Questionnaires , Treatment Outcome
16.
J Vasc Surg ; 32(2): 364-73, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10917997

ABSTRACT

OBJECTIVE: Induced angiogenesis has recently been attempted as a therapeutic modality in patients with occlusive arterial atherosclerotic disease. We investigated the possible role of endogenous opioids in the modulation of angiogenesis. METHODS: Chick chorioallantoic membrane was used as an in vivo model to study angiogenesis. Fertilized chick eggs were incubated for 3 days, explanted, and incubated for an additional 2 days. Three-millimeter methylcellulose disks were placed on the surface of the chorioallantoic membrane; each disk contained opioid growth factor ([Met(5)]-enkephalin; 5 microgram), the short-acting opioid receptor antagonist naloxone (5 microgram), opioid growth factor and naloxone together (5 microgram of each), the long-acting opioid antagonist naltrexone (5 microgram), or distilled water (control). A second series of experiments was performed with distilled water, the angiogenic inhibitor retinoic acid (1 microgram), and vascular endothelial growth factor (1 microgram) to further evaluate our model. The developing vasculature was imaged 2 days later with a digital camera and exported to a computer for image analysis. Total number of blood vessels, total vessel length, and mean vessel length were measured within a 100-mm(2) region surrounding each applied disk. Immunocytochemical analysis was performed with antibodies directed against opioid growth factor and its receptor (OGFr). RESULTS: Opioid growth factor had a significant inhibitory effect on angiogenesis, both the number of blood vessels and the total vessel length being decreased (by 35% and 20%, respectively) in comparison with control levels (P <.005). The simultaneous addition of naloxone and opioid growth factor had no effect on blood vessel growth, nor did naloxone alone. Chorioallantoic membranes exposed to naltrexone displayed increases of 51% and 24% in blood vessel number and length, respectively, in comparison with control specimens (P <.005). These results indicate that the opioid growth factor effects are receptor mediated and tonically active. Immunocytochemistry demonstrated the presence of both opioid growth factor and OGFr within the endothelial cells and mesenchymal cells of the developing chorioallantoic membrane vessel wall. Retinoic acid significantly reduced the number and the total length of blood vessels, whereas vascular endothelial growth factor increased both the number and the length of blood vessels in comparison with the controls (P <.0001). The magnitude of opioid growth factor's effects were comparable to those seen with retinoic acid, whereas inhibition of opioid growth factor with naltrexone induced an increase in total vessel length comparable to that for vascular endothelial growth factor. CONCLUSIONS: These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells.


Subject(s)
Neovascularization, Physiologic/physiology , Opioid Peptides/physiology , Allantois/blood supply , Allantois/drug effects , Animals , Chick Embryo , Chorion/blood supply , Chorion/drug effects , Endothelial Growth Factors/pharmacology , Lymphokines/pharmacology , Naloxone/pharmacology , Neovascularization, Physiologic/drug effects , Opioid Peptides/antagonists & inhibitors , Protein Isoforms/pharmacology , Tretinoin/pharmacology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
17.
Am Surg ; 65(3): 264-5, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10075306

ABSTRACT

Mesenteric cysts are rare intra-abdominal tumors. Most are found during laparotomy for other reasons. The symptoms are often vague and minimal. CT of the abdomen gives the most information and is the diagnostic method of choice. The preferred treatment for mesenteric cysts is complete resection at laparotomy. However, the advancement of minimal-access surgery has allowed laparoscopic excision as a safe and advantageous approach with minimal morbidity and shorter hospital stay and recovery time for the patient.


Subject(s)
Laparoscopy , Mesenteric Cyst/surgery , Adult , Female , Humans
18.
N Engl J Med ; 338(24): 1734-40, 1998 Jun 11.
Article in English | MEDLINE | ID: mdl-9624194

ABSTRACT

BACKGROUND: Homelessness is believed to be a cause of health problems and high medical costs, but data supporting this association have been difficult to obtain. We compared lengths of stay and reasons for hospital admission among homeless and other low-income persons in New York City to estimate the hospitalization costs associated with homelessness. METHODS: We obtained hospital-discharge data on 18,864 admissions of homeless adults to New York City's public general hospitals (excluding admissions for childbirth) and 383,986 nonmaternity admissions of other low-income adults to all general hospitals in New York City during 1992 and 1993. The differences in length of stay were adjusted for diagnosis-related group, principal diagnosis, selected coexisting illnesses, and demographic characteristics. RESULTS: Of the admissions of homeless people, 51.5 percent were for treatment of substance abuse or mental illness, as compared with 22.8 percent for the other low-income patients, and another 19.7 percent of the admissions of homeless people were for trauma, respiratory disorders, skin disorders, and infectious diseases (excluding the acquired immunodeficiency syndrome [AIDS]), many of which are potentially preventable medical conditions. For the homeless, 80.6 percent of the admissions involved either a principal or a secondary diagnosis of substance abuse or mental illness -- roughly twice the rates for the other patients. The homeless patients stayed 4.1 days, or 36 percent, longer per admission on average than the other patients, even after adjustments were made for differences in the rates of substance abuse and mental illness and other clinical and demographic characteristics. The costs of the additional days per discharge averaged $4,094 for psychiatric patients, $3,370 for patients with AIDS, and $2,414 for all types of patients. CONCLUSIONS: Homelessness is associated with substantial excess costs per hospital stay in New York City. Decisions to fund housing and supportive services for the homeless should take into account the potential of these services to reduce the high costs of hospitalization in this population.


Subject(s)
Hospital Costs/statistics & numerical data , Hospitalization/economics , Ill-Housed Persons/statistics & numerical data , Length of Stay/statistics & numerical data , Acquired Immunodeficiency Syndrome/epidemiology , Adolescent , Adult , Aged , Comorbidity , Female , Hospitals, Public/economics , Humans , Length of Stay/economics , Male , Mental Disorders/epidemiology , Middle Aged , New York City , Patient Discharge , Poverty , Substance-Related Disorders/epidemiology
19.
Genome Res ; 7(9): 897-909, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9314495

ABSTRACT

One of the major goals of the human genome project is to establish a physical map of each human chromosome with a density of sequence-tagged site (STS) markers exceeding one every 100 kb. We report here the generation of a human chromosome 5-specific radiation hybrid (RH) map that includes 556 markers. Of these markers, 132 loci are ordered with a maximum likelihood ratio of >1000:1 compared with the next most likely order. An additional 113 loci were ordered relative to these backbone markers with a maximum likelihood ratio of >10:1 but <1000:1. Together, these 245 loci form an ordered framework map for the chromosome. Using this framework, >300 more markers were localized based on two-point analysis with the ordered set. On average, there are 50 markers in common with the RH map presented here and other chromosome 5 maps included in the current whole genome cytogenetic, genetic, and physical maps. The accuracy of all the maps is evident in that there are no more than two discrepancies between any one of them and these data. All of the maps encompassing chromosome 5 complement each other providing excellent STS coverage with >2200 loci combined. The chromosome 5-specific RH map contains 20% of these independent loci. In addition, our RH map contains STSs derived from clones suitable for fluorescent in situ hybridization, allowing alignment to the cytogenetic map. Together, these maps will assist in the assembly of sequence-ready contigs and will aid in the identification of disease loci on chromosome 5 by positional cloning and positional candidate approaches.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 5/ultrastructure , Sequence Tagged Sites , Centromere , Cosmids , Genetic Markers , Humans , Hybrid Cells , In Situ Hybridization, Fluorescence , Likelihood Functions , Lod Score , Molecular Sequence Data , Polymerase Chain Reaction
20.
J Biol Chem ; 269(5): 3539-47, 1994 Feb 04.
Article in English | MEDLINE | ID: mdl-8106396

ABSTRACT

In order to identify protein complexes consisting of the proteasome and specific proteasome regulators, crude soluble lysates of red blood cells were fractionated by gel filtration chromatography and by velocity sedimentation centrifugation. The fractionated lysates were then tested for the relative distribution of proteasome activity, proteasome protein, and protein of a known proteasome activator, PA28. At least two proteasome complexes containing PA28 were identified. One of these complexes had an apparent molecular weight of approximately 1,750,000, and appeared to have much more proteasome activity than could be accounted for by its relative concentrations of proteasome and PA28 protein. We hypothesized that this complex contained another activator of the proteasome, and we sought to purify this activator from extracts of red blood cells. A proteasome activator with an apparent molecular weight of approximately 700,000 was identified, purified, and characterized. This activator, termed PA700, greatly stimulated the peptidase activities of the proteasome in an ATP-dependent fashion. PA700 was composed of about 16 polypeptides ranging in molecular weight from 20,000 to 100,000. The ATP-dependent activation of the proteasome by PA700 was closely linked to the formation of a high molecular weight complex that required no additional ATP for activated proteolysis. These results indicate that PA700 is a regulatory protein of the proteasome and is a component of at least one high molecular weight proteasome-containing complex occurring in cell extracts.


Subject(s)
Blood Proteins/isolation & purification , Blood Proteins/metabolism , Cysteine Endopeptidases/blood , Erythrocytes/metabolism , Multienzyme Complexes/blood , Proteins/isolation & purification , Proteins/metabolism , Adenine Nucleotides/pharmacology , Adenosine Triphosphate/metabolism , Amino Acid Sequence , Animals , Cattle , Chromatography , Chromatography, DEAE-Cellulose , Chromatography, Gel , Cysteine Endopeptidases/isolation & purification , Durapatite , Enzyme Activation , Erythrocytes/enzymology , Kinetics , Molecular Sequence Data , Molecular Weight , Multienzyme Complexes/isolation & purification , Oligopeptides , Proteasome Endopeptidase Complex , Ribonucleotides/pharmacology , Substrate Specificity
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