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1.
Horm Metab Res ; 44(9): 676-81, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22328164

ABSTRACT

Increasing evidence in animal models and in humans shows that sympathetic nerve activity controls ovarian androgen biosynthesis and follicular development. Thus, sympathetic nerve activity participates in the follicular development and the hyperandrogenism characteristics of polycystic ovary syndrome, which is the most prevalent ovarian pathology in women during their reproductive years. In this study, we mimic sympathetic nerve activity in the rat via "in vivo" stimulation with isoproterenol (ISO), a ß-adrenergic receptor agonist, and test for the development of the polycystic ovary condition. We also determine whether this effect can be reversed by the administration of propranolol (PROP), a ß-adrenergic receptor antagonist. Rats were treated for 10 days with 125 µg/kg ISO or with ISO plus 5 mg/kg PROP. The ovaries were examined 1 day or 30 days following drug treatment. While ISO was present, the ovaries had an increased capacity to secrete androgens; ISO + PROP reversed this effect on androgen secretory activity. 30 days after treatment, androstenedione secretion reverted to normal levels, but an increase in the intra-ovarian nerve growth factor (NGF) concentration and luteinizing hormone (LH) plasma levels was detected. ISO treatment resulted in follicular development characterized by an increased number of pre-cystic and cystic ovarian follicles; this was reversed in the ISO + PROP group. The lack of change in the plasma levels of progesterone, androstenedione, testosterone, or estradiol and the increased LH plasma levels strongly suggests a local intra-ovarian effect of ISO indicating that ß-adrenergic stimulation is a definitive component in the rat polycystic ovary condition.


Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Polycystic Ovary Syndrome/drug therapy , Propranolol/administration & dosage , Animals , Disease Models, Animal , Female , Humans , Isoproterenol/adverse effects , Luteinizing Hormone/blood , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/metabolism , Rats , Receptors, Adrenergic, beta/metabolism
2.
Dig Dis ; 26(1): 75-9, 2008.
Article in English | MEDLINE | ID: mdl-18600020

ABSTRACT

BACKGROUND: Several factors could influence patient satisfaction with endoscopy including technical quality of care, comfort and tolerability of the procedure, whether informed consent has been obtained, the level of communication with staff before and after the procedure, and delays in appointments. AIM: To assess what factors should be measured in assessing patient satisfaction by using a 16-point questionnaire based on the informed consent recommendations of the first workshop at Kos, and of the criteria of the American Society for Gastrointestinal Endoscopy (ASGE), and to compare the response of patients with gastroenterologists and the support staff. METHOD: The questionnaire was answered by 81 patients, 71 gastroenterologists and 36 support staff (nurses and receptionists). It graded the relative importance of different factors which influenced the perception of satisfaction in those undergoing endoscopy. These factors included: the waiting time for appointment, the explanation received at various stages before and after the procedure, the reception process, the importance of premedication against pain and discomfort, privacy and satisfaction related to findings at the procedure. RESULTS: Thirteen of the 16 factors were generally graded as important for patient satisfaction. The finding at endoscopy, a written explanation and the alternatives to the endoscopic procedure were regarded as of lesser importance. Gastroenterologists tended to rate the importance of a written explanation and the explanations from the nurses before and after the procedure lower than did the patients and nursing staff. CONCLUSIONS: The courtesy and personal manner of the entire medical staff, as evidenced by the explanation of the procedure by the various physicians before and after and the process of admission, were generally rated of the highest importance. The nurses' ranking of the various factors was closer to that of the patients than of the gastroenterologists.


Subject(s)
Endoscopy , Health Care Surveys , Patient Satisfaction , Humans , Surveys and Questionnaires
3.
Poult Sci ; 87(6): 1171-81, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18493008

ABSTRACT

Previous work in our laboratory showed that including 125 ppm of l-carnitine in the diets of roosters increased sperm concentration. The objective of this experiment was to determine whether reproductive efficiency could be improved by feeding l-carnitine to both parents over that of feeding l-carnitine to only the male or female. Diets formulated to contain 0 or 125 ppm of l-carnitine were fed to male and female birds from hatch until 37 wk of age. Eighty-four roosters were used, with the semen of 2 roosters constituting an experimental unit. Pools of semen from either l-carnitine-supplemented or control roosters were artificially inseminated into each of 288 hens with 23.5 muL of semen at weekly intervals, in a 2 x 2 factorial arrangement, resulting in a mean insemination dose of 1.2 and 1.1 x 10(8) sperm/hen for l-carnitine and control hens, respectively. Dietary l-carnitine, as compared with the control diet, increased egg yolk l-carnitine concentration (P = 0.001), decreased hatchling yolk sac weights (P = 0.0001), decreased yolk sac lipid content at hatch (P = 0.01), and culminated in compositional changes of yolk fatty acids, but it did not affect hatch rate, egg production, and egg traits. Although supplementing diets with l-carnitine improved sperm concentration, it did not result in a subsequent improvement in hatch rate, most likely because of the high numbers of sperm that were inseminated artificially in both the control and l-carnitine-supplemented hens. The higher concentrations of l-carnitine in the yolk of hatching eggs obtained from hens consuming l-carnitine as compared with controls may have encouraged the utilization of fat by developing embryos, as indicated by the decreased hatchling yolk sac weights and yolk sac lipid content, perhaps leading to the selective utilization of linoleic (C18:2n-6) and alpha-linolenic (C18:3n-3) acids for growth and development over myristic (C14:0) and oleic (C18:1n-9) acids.


Subject(s)
Animal Feed , Carnitine/pharmacology , Chickens/physiology , Dietary Supplements , Reproduction/drug effects , Animals , Energy Intake , Female , Male , Sex Characteristics
4.
Poult Sci ; 87(3): 569-72, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18281586

ABSTRACT

Two experiments were conducted to determine if L-carnitine injected in ovo affected hatchability. Eggs of experiment 1 were injected with sterilized saline (0.85%) or L-carnitine (0.25, 0.50, 1.00, or 2.00 micromol dissolved in saline). An additional group of eggs served as noninjected controls. Hatchabilities were unaffected by treatment (94% for noninjected controls; 94% for saline injected eggs; and 87, 87, 88, and 88% for eggs injected with 0.25, 0.50, 1.00, or 2.00 micromol of L-carnitine, respectively; SEM = 1). Yolk sac weights retrieved from hatchings that were subjected to 0, 0.25, or 0.50 micromol of L-carnitine as embryos through in ovo injection were 3.9, 3.8, and 3.6 g, respectively (SEM = 0.1, P = 0.71). Eggs used in experiment 2 were injected with a wider dosimetry of l-carnitine. Fertile eggs were injected with sterilized saline (0.85%) or L-carnitine (0.05, 0.5, 5, or 10 micromol dissolved in saline). An additional group of eggs served as noninjected controls. Chick BW and % hatch were unaffected by treatment (76% for noninjected controls; 74% for saline injected eggs; and 77, 77, 68, and 76% for eggs injected with 0.05, 0.5, 5, or 10 micromol of L-carnitine, respectively; SEM = 3). In ovo injection of L-carnitine into fertile chicken eggs at 17 or 18 d of incubation did not affect hatchability, yolk sac weight, or BW.


Subject(s)
Carnitine/pharmacology , Chick Embryo/drug effects , Chickens/growth & development , Yolk Sac/drug effects , Animals , Body Weight/drug effects , Chick Embryo/growth & development , Dose-Response Relationship, Drug , Egg Yolk , Eggs , Injections/veterinary , Organ Size , Random Allocation
5.
Poult Sci ; 86(10): 2228-35, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17878454

ABSTRACT

A previous study conducted in our laboratory showed that feeding 500 ppm of dietary L-carnitine to young and aging White Leghorns for 5 wk improved sperm concentration and reduced sperm lipid peroxidation during the last half of supplementation. The current study examined the effect of feeding dosimetric as well as lower levels of L-carnitine for longer durations on semen traits of White Leghorns. In experiments 1 and 2, White Leghorns consumed diets supplemented with 0, 125, 250, or 500 mg of L-carnitine/kg of feed. For experiment 1, an 8-wk trial was conducted with 48 White Leghorns from 46 to 54 wk of age. For experiment 2, a 17-wk trial was conducted with 96 White Leghorn roosters from 46 to 63 wk of age. For experiment 3, 84 roosters were provided for ad libitum consumption a diet formulated to contain 0 or 125 ppm of L-carnitine beginning at hatch until 37 wk of age. Long-term consumption of 125 ppm of L-carnitine beginning at hatch was the only dietary treatment that sustained a persistent increase in sperm concentration. These results suggest that L-carnitine's antioxidant influence on sperm production begins before the onset of sexual maturity.


Subject(s)
Carnitine/pharmacology , Chickens/physiology , Diet/veterinary , Semen/drug effects , Aging , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Carnitine/blood , Dietary Supplements , Dose-Response Relationship, Drug , Male
6.
Med Oncol ; 20(1): 87-93, 2003.
Article in English | MEDLINE | ID: mdl-12665689

ABSTRACT

Endometrial stromal sarcoma (ESS) is a rare neoplasm, mainly observed in premenopausal women. We describe two women 44 and 34 years old at the time ESS diagnosis, who developed lung metastases 3 and 6 years, respectively, after initial treatment: hysterectomy without (case 1) or with oophorectomy (case 2), followed by hormone replacement therapy (HRT) for the latter. Their estrogen (ER) and progesterone receptors (PR) were analyzed biochemically in metastatic lung tissue, yielding respective concentrations of ER 242 and 184, and PR 910 and 100 fmol/mg of cytosol protein. Both patients started treatment with the aromatase inhibitor aminoglutethimide (500 mg qid) after surgery for the first patient and after stopping HRT for the second. Under aromatase-inhibitor therapy, both patients achieved a complete response, patient 1 remains disease- free with 14+ years of follow-up, and patient 2 with 7+ years. Our data suggest that an aromatase inhibitor may be an effective treatment for ESS. Furthermore, routine ER and PR analyses could be useful to predict the response to hormonal therapy in ESS.


Subject(s)
Aminoglutethimide/therapeutic use , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Sarcoma, Endometrial Stromal/drug therapy , Sarcoma, Endometrial Stromal/secondary , Adult , Antineoplastic Agents, Hormonal/therapeutic use , Chemotherapy, Adjuvant , Disease-Free Survival , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Enzyme Inhibitors/therapeutic use , Female , Humans , Hysterectomy , Lung Neoplasms/mortality , Ovariectomy , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Remission Induction , Retrospective Studies , Sarcoma, Endometrial Stromal/metabolism , Sarcoma, Endometrial Stromal/mortality , Survival Rate
7.
J Med Screen ; 9(3): 133-4, 2002.
Article in English | MEDLINE | ID: mdl-12370326

ABSTRACT

OBJECTIVE: The purpose of this study was to survey the attitudes of family doctors to the performance of baseline tests and to determine which doctors perform these tests. SETTING: Family physicians in a continuing medical education programme in Tel Aviv, Israel. METHOD: An anonymous questionnaire was distributed focusing on performance of tests by doctors in healthy patients and not as part of a screening programme. RESULTS: Questionnaires were returned by 147 of 165 physicians surveyed (89% response rate). Baseline tests were performed by 98% of respondents: not routinely by 54%, 7% at the patient's request, and 2% did not perform tests. The decision to perform baseline tests was influenced by the presence of other risk factors of disease (86%), patient age (61%), family history (59%), patient request for tests (24%), and patient sex (20%). The tests performed were blood counts, glucose, renal function tests, urinalysis, liver function tests, and electrocardiograms. Baseline tests were useful in case finding of new illnesses for 49% of physicians and 40% said the tests had proved useful during a subsequent illness. The remainder of the physicians found no use for baseline tests. Physicians from the former Soviet Union were more likely to favour baseline tests. CONCLUSION: Almost all of the physicians in this study reported that they perform baseline tests on most of their patients. Evidence based guidelines for these tests and education of physicians are needed.


Subject(s)
Diagnostic Tests, Routine/statistics & numerical data , Family Practice/statistics & numerical data , Mass Screening/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Age Factors , Education, Medical, Continuing , Humans , Israel , Physicians, Family , Risk Factors , Surveys and Questionnaires
8.
Br Poult Sci ; 43(3): 457-64, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12195806

ABSTRACT

1. A relatively new instrument known as a Sperm Quality Analyzer (SQA) offers a rapid assessment of sperm quality and quantity by providing a sperm quality index (SQI). The SQA measures a combination of the intensity of sperm activity and motile concentration by determining the number and amplitude of sperm movements per second in a capillary tube as detected through light beam interference. 2. Because the SQA has not been tested for its potential use in turkeys, the objective was to determine if the SQA could accurately respond to changes in turkey sperm concentration, viability, and motility in semen collected from turkey breeders. 3. The effect of varying concentrations of sperm on SQI values was evaluated by diluting replicate pools of semen from 4 different aged turkey breeder flocks with saline. Results from all 4 flocks showed that semen dilutions greater than 20-fold resulted in a linear decline in SQI values. 4. Additional in vitro analysis evaluated the effects of turkey sperm viability on the SQI under conditions of constant sperm concentration. Incubated, live sperm was mixed in various proportions with thawed, dead sperm to determine changes in viability. Increased proportions of dead sperm caused a decline in the SQI. 5. To assess sperm motility, turkey semen was incubated under either aerobic (motile) or anaerobic (immotile) conditions. Varied amounts of immotile and motile sperm samples were mixed. A linear increase in the SQI was observed as per cent motile sperm increased. 6. These results indicate that the SQA can respond to differences in turkey sperm concentration, viability, and motility using in vitro analyses.


Subject(s)
Semen/physiology , Sperm Count/veterinary , Spermatozoa/physiology , Turkeys/physiology , Animals , Cell Survival , In Vitro Techniques , Male , Semen/chemistry , Semen/cytology , Sperm Count/instrumentation , Sperm Motility , Spermatozoa/cytology
9.
Br Poult Sci ; 43(3): 465-71, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12195807

ABSTRACT

1. A relatively new instrument known as a Sperm Quality Analyzer (SQA) offers a rapid assessment of sperm quality and quantity by providing a sperm quality index (SQI). The SQA measures the intensity of sperm activity and motile concentration by determining the number and amplitude of sperm movements per second in a capillary tube as detected through light beam interference. 2. The objectives of the current study were to determine if the SQA could accurately reflect changes in semen quality that occur with prolonged storage of semen and to determine the variation and change in SQI values among individual breeding male turkeys during their semen production cycle. 3. The effect of storage time on SQI values was evaluated by diluting semen with extender and placing the semen on an oscillating shaker at 4 degrees C for 8 h. The SQI values and sperm viability, expressed as % dead sperm, were recorded hourly. The SQI readings declined linearly with increased storage time while % dead sperm increased linearly with increased semen storage. 4. Semen from 220 individual males was analysed monthly for 9 months. Semen diluted 50-fold with saline had lower SQI values during pre- and post-peak phases of production (months 1, 7, 8, and 9 as compared with months 2 to 6 of semen production). The highest SQI values occurred during months 2 to 6. The largest variation in SQI values occurred during months 1 (CV = 26%) and 9 (CV = 31%) with a CV that averaged 16% for the remaining months. 5. Correlation analysis of SQI values for each bird averaged over 9 months with individual male SQIs for each month showed monthly correlation coefficients that ranged from 0.22 to 0.63. 6. These results indicate that the SQA accurately assessed the decline in sperm quality that occurs with prolonged storage of turkey semen and reflected age-related changes in semen quality and quantity that occurred during a semen production cycle of turkey breeders. In addition, the semen quality rank of some turkey breeders in a population changed with age.


Subject(s)
Aging/physiology , Semen/physiology , Spermatozoa/physiology , Turkeys/physiology , Animals , Cell Survival , Male , Semen/chemistry , Semen/cytology , Semen Preservation , Sperm Count/instrumentation , Sperm Count/veterinary , Sperm Motility , Spermatozoa/cytology , Time Factors
10.
Poult Sci ; 81(4): 495-503, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11989749

ABSTRACT

Carnitine has antioxidant properties that protect sperm membranes against toxic reactive oxygen species. Carnitine also functions to reduce the availability of lipids for peroxidation by transporting fatty acids into the mitochondria for beta-oxidation to generate adenosine triphosphate (ATP) energy. Because the effects of this supplemental amino acid on the reproductive performance of the avian breeder male are unknown, the objective of the current study was to evaluate the antioxidant role of dietary L-carnitine on semen traits and testicular histology in Leghorn breeder roosters. Two experiments were conducted in which birds were fed a control diet or one supplemented with 500 mg of carnitine/kg of diet. For Experiment 1, dietary treatments were fed to older birds (n = 12 birds/treatment) when they were 58 to 62 wk of age. For Experiment 2, younger birds were fed dietary treatments between 32 to 37 wk of age (n = 14 experimental units/treatment with three roosters composing an experimental unit for a total of 84 roosters). Semen traits and lipid peroxidation of sperm, determined by measuring malonaldehyde, were examined weekly. Feeding dietary carnitine to young and aging White Leghorn roosters ad libitum for 5 wk not only improved sperm concentration during the last half of supplementation but also reduced sperm lipid peroxidation. Testicular tissue of birds fed dietary carnitine for 5 wk was preserved as indicated by a reduction in multinucleated giant cells. These results suggest that dietary carnitine has antioxidant properties that may preserve sperm membranes in roosters, thereby extending the life span of sperm.


Subject(s)
Antioxidants/administration & dosage , Carnitine/administration & dosage , Chickens/physiology , Semen/drug effects , Aging/physiology , Animals , Antioxidants/pharmacology , Carnitine/pharmacology , Chickens/anatomy & histology , Chickens/metabolism , Giant Cells , Lipid Peroxidation/drug effects , Male , Malondialdehyde/analysis , Oxidation-Reduction , Reactive Oxygen Species , Semen/physiology , Testis/cytology , Testis/drug effects
11.
Poult Sci ; 81(2): 265-8, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11873837

ABSTRACT

A 9-mo field trial was conducted to evaluate the effects of dietary L-ascorbic acid (AA) on semen traits of 144 male turkey breeders. Dietary AA treatments were initiated when birds were 30 wk of age. Semen and blood collection began at 32 wk of age. Three treatments with four pens per treatment and 12 birds per pen were fed 0, 75, and 150 mg/kg AA during the first 4 mo of their reproductive cycle. Levels of AA were doubled in the supplemented diets to 150 and 300 mg/kg during Months 5 to 9. Semen traits and blood AA were unaffected by dietary AA. When birds were 65 wk of age, testes were removed from 12 birds per treatment for histological analysis. Multinucleated giant cells (MCG), indicative of degeneration, were observed in the testes of 7 of the 12 control birds but were absent from AA-supplemented birds (P < 0.02). The antioxidant properties of AA may delay formation of these degenerative cells. In conclusion, dietary AA levels employed in the current study did not affect semen traits or testis weight but were associated with reduced formation of MGC in the testes of 65 wk-old breeder toms.


Subject(s)
Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Diet , Semen/physiology , Testis/cytology , Turkeys/anatomy & histology , Turkeys/physiology , Animals , Ascorbic Acid/blood , Body Weight , Cell Survival , Giant Cells , Male , Semen/drug effects , Sperm Count , Testis/drug effects
12.
Ground Water ; 39(5): 685-95, 2001.
Article in English | MEDLINE | ID: mdl-11554246

ABSTRACT

A numerical inverse method was used to interpret simultaneously multirate injection and recovery data from single-hole pneumatic tests in unsaturated fractured tuff at the Apache Leap Research Site near Superior, Arizona. Our model represents faithfully the three-dimensional geometry of boreholes at the site, and accounts directly for their storage and conductance properties by treating them as high-permeability and high-porosity cylinders of finite length and radius. It solves the airflow equations in their original nonlinear form and yields information about air permeability, air-filled porosity and dimensionless borehole storage coefficient. Some of this is difficult to accomplish with analytical type-curves. Air permeability values obtained by our inverse method agree well with those obtained by steady-state and type-curve analyses.


Subject(s)
Models, Theoretical , Soil , Air , Geological Phenomena , Geology , Permeability , Porosity , Water Movements
13.
Gene ; 263(1-2): 17-29, 2001 Jan 24.
Article in English | MEDLINE | ID: mdl-11223239

ABSTRACT

The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest known gene containing at least 79 introns, some of which are extremely large. The product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene encodes at least two additional non-muscle full length dystrophin isoforms transcribed from different promoters located in the 5'-end region of the gene, and four smaller proteins transcribed from internal promoters located further downstream, and lack important domains of dystrophin. Several other genes, encoding evolutionarily related proteins, have been identified. To study the evolution of the DMD gene and the significance of its various products, we have searched for genes encoding dystrophin-like proteins in sea urchin and in Drosophila. We previously reported on the characterization of a sea urchin gene encoding a protein which is an evolutionary homologue of Dp116, one of the small products of the mammalian DMD gene, and on the partial sequencing of a large product of the same gene. Here we describe the full-length product which shows strong structural similarity and sequence identity to human dystrophin and utrophin. We also describe a Drosophila gene closely related to the human dystrophin gene. Like the human gene, the Drosophila gene encodes at least three isoforms of full length dystrophin-like proteins (dmDLP1, dmDLP2 and dmDLP3,), regulated by different promoters located at the 5' end of the gene, and a smaller product regulated by an internal promoter (dmDp186). As in mammals, dmDp186 and the dmDLPs share the same C-terminal and cysteine-rich domains which are very similar to the corresponding domains in human dystrophin and utrophin. In addition, dmDp186 contains four of the spectrin-like repeats of the dmDLPs and a unique N-terminal region of 512 amino acids encoded by a single exon. The full length products and the small product have distinct patterns of expression. Thus, the complex structure of the dystrophin gene, encoding several large dystrophin-like isoforms and smaller truncated products with different patterns of expression, existed before the divergence between the protostomes and deuterostomes. The conservation of this gene structure in such distantly related organisms, points to important distinct functions of the multiple products.


Subject(s)
Cytoskeletal Proteins/genetics , Drosophila/genetics , Dystrophin/genetics , Membrane Proteins/genetics , Sea Urchins/genetics , Alternative Splicing , Amino Acid Sequence , Animals , Chromosome Mapping , DNA/chemistry , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Drosophila/embryology , Drosophila/growth & development , Embryo, Nonmammalian/metabolism , Exons , Gene Expression Regulation, Developmental , Genes, Insect/genetics , Humans , In Situ Hybridization , Introns , Molecular Sequence Data , Muscular Dystrophy, Duchenne/genetics , Phylogeny , RNA, Messenger/genetics , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Transcription, Genetic , Utrophin
14.
Gene ; 185(1): 99-103, 1997 Jan 31.
Article in English | MEDLINE | ID: mdl-9034319

ABSTRACT

A mouse testis cDNA expression library (Clontech) was screened with a synthetic oligonucleotide ligand containing CT-rich motifs derived from the rat skeletal muscle actin gene promoter. These motifs bind nuclear proteins, and seem to be involved in the regulation of the gene. Analysis of isolated clones, which expressed proteins that specifically bind the oligonucleotide, indicated that they were derived from a single gene. This gene was identified as a contaminant of bacterial origin (Leuconostoc lactis). The cloned gene from L. lactis encodes a protein with significant homology to bacterial ribosomal protein S1, which we designated LrpS1-L. Band shift analysis and competition experiments indicated that both the bacterial protein and a mouse nuclear protein specifically bind to the same CT-rich motif of the skeletal muscle actin promoter. Furthermore, antibodies against the recombinant bacterial protein interfered with the formation of complex between the CT-rich element and the mouse nuclear protein. These results indicate that the bacterial LrpS1-L protein and the mammalian protein bind the same CT-rich motif and share common antigenic epitopes.


Subject(s)
Actins/genetics , Bacterial Proteins/genetics , Bacterial Proteins/immunology , DNA, Complementary/genetics , DNA-Binding Proteins/genetics , Epitopes/immunology , Leuconostoc/genetics , Muscle, Skeletal/chemistry , Promoter Regions, Genetic , Ribosomal Proteins/genetics , Ribosomal Proteins/immunology , Animals , Antibodies, Bacterial , Antibodies, Blocking , Base Sequence , Blotting, Northern , Blotting, Southern , Blotting, Western , Cloning, Molecular , Gene Library , Male , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Protein Binding/genetics , Rats , Recombinant Proteins/immunology , Sequence Analysis, DNA , Sequence Analysis, RNA , Testis/chemistry
15.
Cancer Radiother ; 1(2): 121-31, 1997.
Article in French | MEDLINE | ID: mdl-9273182

ABSTRACT

PURPOSE: To determine the efficacy and safety of induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of stage III non-small cell lung cancer and whether the response to induction chemotherapy can predict the response to subsequent chemoradiotherapy and survival. MATERIALS AND METHODS: Between December 1987 and June 1993, 46 patients with previously untreated stage III non-small cell lung cancer received every 21 days induction chemotherapy (ICT) including three cycles of 5-fluorouracil (600 mg/m2/d in short infusion from d1 to d5), cisplatin (15 mg/m2/d from d1 to d5), etoposide (50 mg/m2/d from d1 to d5) and hydroxyurea (1,500 mg/d from d1 to d5). The first 21 patients also received bleomycin (3 mg/m2/d from d1 to d5). All patients received concomitant chemotherapy and had chest radiotherapy (CCRT). Patients received irradiation (65 Gy/33-6 fractions/7 weeks) on d25 after the third cycle of chemotherapy. Concomitant chemotherapy was composed of cisplatin (20 mg/m2) and 5-fluorouracil (500 mg/m2) that were administered each Monday and Thursday during radiotherapy. Maintenance chemotherapy consisted of thiotepa (10 mg/m2) and methotrexate (10 mg/m2) that were administered every 2 weeks for 6 months. RESULTS: Pulmonary toxicity was observed in four out of 21 patients who had received bleomycin and subsequently developed pulmonary fibrosis, leading to death for two of them. ICT alone produced five complete responses (11%) and 13 partial responses (28%). The combination of chemotherapy and radiotherapy led to 19 complete responses (41%) and 14 partial responses (30%). Eighteen of the 18 responders (100%) to ICT responded to subsequent CCRT, of whom 13 (72%) became complete responders. Fifteen of the 28 non-responders to ICT (53%) responded to CCRT, six of them being complete responders (21%) (P < 0.001). The median overall survival rate was 17 months when considering all patients, 25 months in patients responding to ICT and 13 months in non-responders. The 2-year survival rates were 28, 55 and 11%, respectively (P < 0.05). ICT did not influence the rate of subsequent metastatic events. However, locoregional reprogression was lower in responders to ICT. The number of metastatic events was not significantly related to response to ICT. By contrast, the rate of local failure was higher when there was resistance to ICT (75% versus 39%). Out of the 19 complete responders to CCRT (13 responders to ICT and six non-responders to ICT), four developed secondary locoregional reprogression (21%) and six developed metastatic disease (31%). In complete responders to CCRT, the rate of locoregional failure was 15% in responders to ICT (2/13) and 33% (2/6) in non-responders to ICT. Four out of the 13 responders to CCRT after response to ICT (31%) and two out of the six complete responders to CCRT developed metastatic disease after non-response to ICT. CONCLUSION: There is a statistically significant relationship not only between the response to ICT and the response to CCRT, but also between the response to ICT and the local outcome and survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Bronchogenic/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Bronchogenic/pathology , Carcinoma, Bronchogenic/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Drug Administration Schedule , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Radiotherapy Dosage , Survival Rate
16.
Genes Dev ; 8(8): 959-69, 1994 Apr 15.
Article in English | MEDLINE | ID: mdl-7926780

ABSTRACT

Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in Suffolk sheep, and within this breed 49 +/- 6% (+/- S.D., n = 69) of healthy animals carry one or more PrP alleles encoding Arg (R)-171. Four scrapie-affected sheep were homozygous for wild-type PrP open reading frames encoding the alternative Gln (Q)-171 allele. Analysis of additional cases revealed that all were Q/Q-171 homozygotes (n = 31), yielding a probability of 0.000004 that PrP genotype is unrelated to susceptibility. These data imply that homozygosity for Q-171 codons is necessary but not sufficient for the development of natural scrapie, echo reports of recessive manifestation, and parallel over-representation of PRNP codon 129 homozygotes in Creutzfeldt-Jakob disease of humans. Whereas progress has been substantial regarding experimental scrapie in rodents, the occurrence and spread of disease in flocks of sheep has remained enigmatic. Appreciation of the relationship between codon 171 genotype and susceptibility may help define the molecular basis of natural scrapie.


Subject(s)
PrPSc Proteins/genetics , Scrapie/etiology , Scrapie/genetics , Alleles , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Exons/genetics , Female , Genetic Predisposition to Disease , Glutamine/genetics , Homozygote , Male , Models, Genetic , Molecular Sequence Data , Polymorphism, Genetic , Promoter Regions, Genetic/genetics , Scrapie/epidemiology , Scrapie/prevention & control , Sequence Analysis, DNA , Sheep , Species Specificity , United States/epidemiology
17.
J Popul Econ ; 6(1): 57-66, 1993.
Article in English | MEDLINE | ID: mdl-12285975

ABSTRACT

PIP: The kibbutz is a uniquely socially organized entity that consists of members having equal consumption possibilities, which are not tied to production. There are no wages and child rearing is performed outside the family unit. A theoretical model is presented which explains the differences between fertility in the kibbutz and in the city, and which is tested with data from the 1983 Israeli Census of Population and Housing. The model includes family consumption, the number of children, the time a parent works, years of finished schooling, duration of marriage, wages, and the time a parent cares for own children. The sample population only considers first marrieds with both spouses present, where the wife is at least 35 years old: 77,455 urban families and 2532 kibbutz families. The results of the ordinary least squares analysis indicate that socioeconomic variables explain fertility in the city much better. Regressions which include oriental origin show that women of oriental origin have 1.663 more children in the city and .343 more children in the kibbutz than Western women. Only 10% of the kibbutzim (plural of kibbutz) had an oriental background, while 40% had an oriental background in the city in 1983. Other control variables were immigration status and duration of marriage. The effect of mother's education shows the number of children decreasing with education until reaching a minimum of 13.9 years, or 14.5 years for mother's education and 10.5 years for father's education in the city. Parents' education is insignificant in the kibbutz. Father's ethnicity affects fertility in the city, but mother's ethnicity affects fertility in the kibbutz. Mother's predicted wage is added to her education; the results show a positive effect in both the city and kibbutz, which shows a larger effect. The reason is that education is more valuable in the city in securing work. Regressions with fathers' ages and education indicate that fathers' predicted wages is positive in both places. Mothers' predicted wages remains positive, but is less than fathers' preducted wages. Parents' education shows a negative effect in the city and a small negative effect or no effect in the kibbutz.^ieng


Subject(s)
Economics , Educational Status , Ethnicity , Fertility , Income , Marriage , Models, Theoretical , Parents , Research , Residence Characteristics , Salaries and Fringe Benefits , Social Behavior , Urban Population , Asia , Asia, Western , Behavior , Culture , Demography , Developed Countries , Family Characteristics , Family Relations , Geography , Israel , Population , Population Characteristics , Population Dynamics , Social Class , Socioeconomic Factors
18.
Surgery ; 109(3 Pt 1): 244-51, 1991 Mar.
Article in English | MEDLINE | ID: mdl-2000555

ABSTRACT

This study analyzed 33 variables that might potentially affect outcome in a series of 332 consecutive elective abdominal aortic aneurysm repairs in a southern West Virginia community. One of the interesting features of this series was that the repairs were done by 22 surgeons with varying degrees of experience. The mortality and complication rates were compared for various potential risk factors by both univariant methods (chi 2, Fisher's exact, and Student t tests) and multivariant methods of analysis. Our early mortality (2.1%) and postoperative complication rates were consistent with those of other series. With multiple linear regression models, five factors were selected as significant independent risk factors associated with an increasing number of postoperative complications: the number of blood transfusions (p less than 0.0001), left renal vein ligation (p less than 0.0001), the presence of greater than 50% renal artery stenosis (p = 0.0012), the lesser experience of the surgeon (p = 0.0203), and the history of prior cardiac catheterization (p = 0.0245). The only factor statistically correlated with mortality rate was an increased number of postoperative complications (p less than 0.0001). Neither postoperative complications nor mortality rate was found to be significant and independently influenced by other demographic, clinical, or operative factors. It is tempting to speculate that surgeons with less experience might be well served to refer patients with significant renal artery stenosis and coronary artery disease. Our mortality and complication rates were not increased by performing preoperative angiography and therefore prudent surgeons may find this helpful in selecting patients for safer repair.


Subject(s)
Aortic Aneurysm/surgery , Aged , Analysis of Variance , Aorta, Abdominal , Aortic Aneurysm/mortality , Female , Humans , Male , Multivariate Analysis , Postoperative Complications , Regression Analysis , Retrospective Studies , Risk Factors , West Virginia
19.
Biochem J ; 272(2): 557-60, 1990 Dec 01.
Article in English | MEDLINE | ID: mdl-2176467

ABSTRACT

A novel transcript of the Duchenne muscular dystrophy gene has been identified. This 6.5 kb mRNA contains sequences from the 3' untranslated region of dystrophin mRNA and from the regions coding for the C-terminal and the cysteine-rich domains. However, probes for the regions encoding the spectrin-like repeats and the actin-binding domain, as well as probes for the first exons of the muscle- and brain-type dystrophin mRNA, did not hybridize with this new mRNA. Significant amounts of the 6.5 kb mRNA were found in a variety of non-muscle tissues, such as liver, testis, lung and kidney, but not in skeletal muscle. The abundance of this mRNA in the brain is at least as high as that of the previously described 14 kb brain-type dystrophin mRNA.


Subject(s)
Dystrophin/genetics , Genetic Variation , Muscles/metabolism , Muscular Dystrophies/genetics , RNA, Messenger/genetics , Animals , Brain/metabolism , Carcinoma, Hepatocellular , Cell Line , Genes , Humans , Liver Neoplasms , Male , Nucleic Acid Hybridization , Organ Specificity , RNA Splicing , Rats , Spectrin/genetics , Transcription, Genetic
20.
Nature ; 337(6202): 76-8, 1989 Jan 05.
Article in English | MEDLINE | ID: mdl-2909892

ABSTRACT

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting in progressive degeneration of the muscle. It affects about 1 in 3,500 male children. Becker's muscular dystrophy is a less severe disease allelic to DMD. Some 30% of DMD patients suffer from various degrees of mental retardation. The giant DMD gene spans about 2,000 kilobases and codes for a 14-kilobase messenger RNA and a protein of molecular weight 427,000. DMD mRNA is most abundant in skeletal and cardiac muscle and less so in smooth muscle. We reported that the expression of the gene is developmentally regulated during the differentiation of primary muscle cultures and in myogenic cell lines in a way similar to the expression of muscle-specific genes such as myosin light chain 2 and skeletal muscle actin. Similar results have been obtained with human primary myogenic cells. Significant levels of DMD mRNA are found in brain tissue. Here we show that the transcript of the DMD gene and the amino terminal of the encoded protein differ in brain and muscle. The 5' ends of these mRNA species are derived from different exons. The results suggest that the two mRNA types are transcribed from different promoters.


Subject(s)
Brain Chemistry , Muscles/analysis , Muscular Dystrophy, Animal/genetics , RNA, Messenger/analysis , Animals , Base Sequence , Molecular Sequence Data , RNA Probes , Rats
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