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1.
Rev. chil. radiol ; 24(4): 129-133, dic. 2018. ilus
Article in Spanish | LILACS | ID: biblio-978168

ABSTRACT

El objetivo de este estudio es la descripción de la novedosa y poco invasiva técnica de marcación de pequeños nódulos pulmonares con lipiodol, guiado con TAC para su posterior resección por cirugía videotoracoscópica con apoyo radioscópico. Se trata de un estudio retrospectivo que incluye 51 pacientes consecutivos en un tiempo comprendido entre junio del 2012 a septiembre del 2017, obteniendo el diagnóstico final mediante la correlación anatomopatológica, representando los procesos malignos el 81% y los benignos el 19%. Mediante esta técnica se lograron identificar y extraer con éxito el 100% de los nódulos marcados, demostrándose la efectividad y seguridad del procedimiento por las mínimas complicaciones relacionadas.


The purpose of this study is describing a novel and minimally invasive technique of CT-guided marking of small pulmonary nodules with lipiodol prior to resection by videothoracoscopic surgery with radioscopic support. This is a retrospective study that includes 51 consecutive patients between June 2012 and September 2017, with the final diagnosis confirmed by pathology. Malignant nodules represented 81% of the cases with the remaining 19% being benign nodules. Through this technique, 100% of the marked nodules were successfully identified and extracted with few procedure related complications and no adverse clinical outcome, demonstrating the effectiveness and safety of the procedure.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Solitary Pulmonary Nodule/surgery , Solitary Pulmonary Nodule/diagnostic imaging , Ethiodized Oil/administration & dosage , Thoracic Surgery, Video-Assisted/methods , Lung Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Retrospective Studies , Solitary Pulmonary Nodule/pathology , Contrast Media/administration & dosage , Lung Neoplasms/pathology
3.
Gastroenterol. latinoam ; 25(1): 9-16, 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-765143

ABSTRACT

Background: Perianal fistula (PF) may be present in 40 percent of patients with Crohn´s Disease (CD). Due to its complexity, its management should be multidisciplinary. Purpose: To describe clinical treatment in patients with CD and PF in our institution. Materials and Methods: This is a descriptive retroprospective study, using a registry of CD patients. We selected patients with PF and further characterized those patients that received their treatment at Clínica las Condes (CLC). Results: From a total of 74 patients with CD in the registry, 23 (31 percent) had PF, 61 percent male, median of 7 years of disease and half with colonic extension. Twelve patients were treated in CLC, from these, seven had concomitant proctitis. Optimal diagnostic study (magnetic resonance imaging/endorectal ultrasound plus examination under anesthetic) was performed in eleven (92 percent) patients. Ten (83 percent) patients received an optimal treatment (drainage and installation of a loose seton + start or optimization of medical therapy). Complete clinical response was achieved in more than half of the patients under optimal treatment within the first 6 months. Six (50 percent) patients had one or more recurrences of PF with similar study and management in a median of 13 months. With a median follow-up of 29 months, eight out of 12 patients had complete clinical response. There was one patient with unfavorable course who required a proctectomy and terminal diversion. Conclusion: Treatment of PF in CD is complex and in our population, the first-line treatment includes the installation of a loose seton and medical therapy to achieve clinical response even though fistulous tracts may persist.


Introducción: La fístula perianal (FP) puede presentarse hasta en 40 por ciento de los pacientes con Enfermedad de Crohn (EC). Dada su complejidad el tratamiento debe ser multidisciplinario. Objetivo: Describir el tratamiento de los pacientes portadores de EC con FP. Métodos: Estudio descriptivo, utilizando un registro de pacientes con EC. Se seleccionaron los pacientes con FP y se caracterizaron aquellos que recibieron el tratamiento en Clínica Las Condes (CLC). Resultados: De un total de 74 pacientes con EC, 23 (31 por ciento) presentaban FP asociada, 61 por ciento de sexo masculino, mediana de duración de enfermedad 7 años y la mitad con extensión colónica. Doce pacientes fueron tratados en CLC, de ellos, siete presentaban proctitis al momento de la FP. En 11 (92 por ciento) pacientes se realizó un estudio diagnóstico óptimo (resonancia magnética/ endosonografía transrrectal y exploración bajo anestesia). Diez (83 por ciento) pacientes recibieron tratamiento óptimo biasociado (drenaje e instalación de sedal no cortante + inicio u optimización de terapia médica). Siete pacientes con tratamiento óptimo presentaron mejoría clínica completa dentro de los primeros 6 meses. Seis (50 por ciento) pacientes presentaron una o más recurrencia de FP con estudio y manejo similar en una mediana de 13 meses. Con una mediana de seguimiento de 29 meses, ocho de los 12 pacientes obtuvieron mejoría clínica completa. Una paciente evolucionó desfavorablemente, requiriendo proctectomía y ostomía terminal. Conclusión: El manejo del FP en EC es complejo, en nuestra población el tratamiento biasociado (sedal + fármacos) fue de elección para lograr una mejoría clínica aun cuando persistieron los trayectos fistulosos.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Crohn Disease/complications , Rectal Fistula/etiology , Rectal Fistula/therapy , Antibodies, Monoclonal/therapeutic use , Azathioprine/therapeutic use , Biological Therapy , Combined Modality Therapy , Anal Canal/pathology , Drainage/methods , Crohn Disease/therapy , Follow-Up Studies , Retrospective Studies , Treatment Outcome
4.
Knee ; 20(6): 442-6, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23777807

ABSTRACT

BACKGROUND: Despite the excellent total knee arthroplasty (TKA) results reported using traditional outcome measures, dissatisfaction rates of up to 30% are reported following surgery. Although several preoperative factors have been identified as possible predictors of satisfaction, there is conflicting evidence. Identification of dissatisfaction in the early postoperative assessment may therefore be an alternative consideration. METHODS: We examined the relationship between 12-month satisfaction, and early post-operative outcomes in a cohort of 486 TKA patients. Preoperative, and postoperative outcome measures at 3- and 12-months (Oxford knee score, pain score, SF12, and knee motion), were analysed and compared between patients who were satisfied and dissatisfied at 12-months following TKA. Mean scores, and postoperative change in scores were calculated. Postoperative outcomes were examined for correlation with satisfaction, and multivariate logistic regression models used to identify potential predictors of dissatisfaction. RESULTS: Overall satisfaction was 77.0%. No preoperative differences were observed between groups. Dissatisfaction was associated with worse postoperative status across all outcome measures (p<0.001), except the 3-month SF12-physical component (p=0.052). Dissatisfied patients demonstrated minimal further improvement or even worsening of outcome scores between 3- and 12-months postoperatively (p<0.02). Both the 3-month OKS (OR=1.15, p<0.001), and knee flexion (OR=1.03, p=0.009) were significant predictors of subsequent 12-month satisfaction. CONCLUSIONS: Dissatisfaction following TKA is associated with worse outcomes as early as 3months following surgery, with minimal further improvement subsequently achieved at 12-months. Early postoperative assessment following TKA should therefore be considered, including clinical assessment, to identify those patients at risk of dissatisfaction.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Osteoarthritis, Knee/surgery , Patient Satisfaction/statistics & numerical data , Range of Motion, Articular/physiology , Aged , Arthroplasty, Replacement, Knee/adverse effects , Databases, Factual , Female , Follow-Up Studies , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Osteoarthritis, Knee/diagnostic imaging , Pain Measurement , Pain, Postoperative/physiopathology , Postoperative Period , Predictive Value of Tests , Prospective Studies , Quality of Life , Radiography , Severity of Illness Index , Time Factors , Treatment Outcome
5.
Proc Nutr Soc ; 70(1): 135-43, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21092367

ABSTRACT

Taste is often cited as the factor of greatest significance in food choice, and has been described as the body's 'nutritional gatekeeper'. Variation in taste receptor genes can give rise to differential perception of sweet, umami and bitter tastes, whereas less is known about the genetics of sour and salty taste. Over twenty-five bitter taste receptor genes exist, of which TAS2R38 is one of the most studied. This gene is broadly tuned to the perception of the bitter-tasting thiourea compounds, which are found in brassica vegetables and other foods with purported health benefits, such as green tea and soya. Variations in this gene contribute to three thiourea taster groups of people: supertasters, medium tasters and nontasters. Differences in taster status have been linked to body weight, alcoholism, preferences for sugar and fat levels in food and fruit and vegetable preferences. However, genetic predispositions to food preferences may be outweighed by environmental influences, and few studies have examined both. The Tastebuddies study aimed at taking a holistic approach, examining both genetic and environmental factors in children and adults. Taster status, age and gender were the most significant influences in food preferences, whereas genotype was less important. Taster perception was associated with BMI in women; nontasters had a higher mean BMI than medium tasters or supertasters. Nutrient intakes were influenced by both phenotype and genotype for the whole group, and in women, the AVI variation of the TAS2R38 gene was associated with a nutrient intake pattern indicative of healthy eating.


Subject(s)
Dysgeusia/genetics , Food Preferences/physiology , Genetic Variation , Taste Perception/genetics , Taste/genetics , Age Factors , Body Mass Index , Dysgeusia/complications , Energy Intake/genetics , Genotype , Humans , Phenotype , Sex Factors
8.
J Am Coll Nutr ; 20(5): 477-84, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11601562

ABSTRACT

OBJECTIVE: To investigate the efficacy of, first, a dietary regimen involving increased consumption of iron-rich foods and enhancers of iron absorption and decreased consumption of inhibitors of iron absorption and, second, a low dose iron chelate iron supplement, for increasing iron stores in young adult New Zealand women with mild iron deficiency (MID). METHODS: The study was a 16 week randomized placebo-controlled intervention. Seventy-five women aged 18 to 40 years with MID (serum ferritin < 20 microg/L and hemoglobin > or = 120 g/L) were assigned to one of three groups: Placebo, Supplement (50 mg iron/day as amino acid chelate) or Diet. Participants in the Diet Group were given individual dietary counseling to increase the intake and bioavailability of dietary iron. Dietary changes were monitored by a previously validated computer-administered iron food frequency questionnaire. RESULTS: Diet Group members significantly increased their intake of flesh foods, heme iron, vitamin C and foods cooked using cast-iron cookware and significantly decreased their phytate and calcium intakes. Serum ferritin increased in the Supplement and Diet Groups by 59% (p=0.001) and 26% (p=0.068), respectively, in comparison to the Placebo Group. The serum transferrin receptor:serum ferritin ratio decreased by 51% in the Supplement Group (p=0.001), and there was a non-significant decrease of 22% (p=0.1232) in the Diet Group. CONCLUSIONS: This study is the first, to our knowledge, to demonstrate that an intensive dietary program has the potential to improve the iron status of women with iron deficiency.


Subject(s)
Ascorbic Acid/administration & dosage , Iron Chelating Agents/administration & dosage , Iron Deficiencies , Iron, Dietary/administration & dosage , Iron/pharmacokinetics , Adolescent , Adult , Calcium, Dietary/administration & dosage , Cooking , Cooking and Eating Utensils , Diet Therapy , Dietary Supplements , Double-Blind Method , Female , Ferritins/blood , Humans , Intestinal Absorption , Nutritional Status , Phytic Acid/administration & dosage , Surveys and Questionnaires , Treatment Outcome
9.
Hum Exp Toxicol ; 19(4): 230-43, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10918514

ABSTRACT

The preclinical safety assessment of biopharmaceuticals necessitates that studies be conducted in species in which the products are pharmacologically active. Monoclonal antibodies are a promising class of biopharmaceuticals for many disease indications; however, by design, these agents tend to have limited species cross-reactivity and tend to only be active in primates. Keliximab is a human-cynomolgus monkey chimeric (Primatized) monoclonal antibody with specificity for human and chimpanzee CD4. In order to conduct a comprehensive preclinical safety assessment of this antibody to support chronic treatment of rheumatoid arthritis in patients, a human CD4 transgenic mouse was used for chronic and reproductive toxicity studies and for genotoxic studies. In addition, immunotoxicity studies were conducted in these mice with Candida albicans, Pneumocystis carinii and B16 melanoma cells to assess the effects of keliximab on host resistance to infection and immunosurveillance to neoplasia. The results of these studies found keliximab to be well tolerated with the only effects observed being related to its pharmacologic activity on CD4+ T lymphocytes. The use of transgenic mice expressing human proteins provides a useful alternative to studies in chimpanzees with biopharmaceutical agents having limited species cross-reactivity.


Subject(s)
Antibodies, Monoclonal/toxicity , CD4 Antigens/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Antibody Formation/drug effects , CHO Cells , Candidiasis/immunology , Cricetinae , Drug Evaluation, Preclinical , Female , Flow Cytometry , Humans , Hypersensitivity, Delayed/immunology , Immune System/growth & development , In Situ Hybridization, Fluorescence , Lymphocyte Culture Test, Mixed , Male , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Mice , Mice, SCID , Mice, Transgenic , Micronucleus Tests , Pneumocystis Infections/immunology , Reproduction/drug effects
10.
Clin Invest Med ; 23(2): 124-31, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10852662

ABSTRACT

OBJECTIVE: To test the efficacy of chelation therapy, an alternative medical treatment, as an antiatherosclerotic procedure, using an animal model of insulin resistance and vascular disease. DESIGN: A prospective animal experiment with procedures modelled on human chelation treatments. SUBJECTS: The JCR:LA-cp rat, a strain that, if homozygous for the autosomal recessive cp gene, becomes obese and insulin resistant, with marked hyperinsulinemia and hypertriglyceridemia, and is unique in the spontaneous development of atherosclerosis and ischemic myocardial lesions. EXPERIMENTAL PROTOCOL: Eight-month-old, obese, male JCR:LA-cp rats were fitted with indwelling venous cannulae and infused over 4 weeks with ethylenediaminetetraacetic acid (EDTA) 5 days a week at a daily dose of 40 mg/kg body weight. At the end of the treatment period, samples were taken for assay of blood parameters and for mineral content of bone. The rats were sacrificed and perfusion-fixed for scanning electron microscopy of the aortic arch. RESULTS: Plasma cholesterol concentrations were not changed by the EDTA treatment. In contrast, plasma triglyceride concentrations were raised significantly (74%, p < 0.05). Lean control rats showed minimal abnormality of the aortic arch, whereas the obese control rats had raised intimal lesions, frequent adherent macrophages and endothelial damage. The frequency of these vascular abnormalities in the EDTA-treated rats was not different from that seen in the obese controls. The bone contents of calcium and magnesium were not significantly reduced. CONCLUSIONS: Chelation therapy using intravenous EDTA has no beneficial effects on the arterial lesions in the atherosclerotic JCR:LA-cp rat. The increase in plasma triglyceride concentrations would be grounds for concern in human patients.


Subject(s)
Arteriosclerosis/drug therapy , Chelation Therapy , Disease Models, Animal , Edetic Acid/therapeutic use , Animals , Aorta, Thoracic/pathology , Bone and Bones/chemistry , Calcium/analysis , Complementary Therapies , Edetic Acid/administration & dosage , Endothelium, Vascular/pathology , Insulin Resistance/genetics , Lipids/blood , Macrophages/pathology , Magnesium/analysis , Male , Microscopy, Electron, Scanning , Obesity/genetics , Prospective Studies , Rats , Rats, Mutant Strains , Triglycerides/blood
11.
Am Surg ; 65(4): 303-6, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10190350

ABSTRACT

A home health care (HHC) referral should link the patient in a cost-effective fashion to the physician, home care, and instructions regarding ulcer management. Twenty-one patients (mean age, 74.6 years) had stage III pressure ulcers (<100 cm2) and an involved family member at home. Risk and contributing factors included cardiac disease (n = 9), hypertension (n = 14), end-stage renal disease (n = 7), smoking (n = 11), diabetes (n = 8), chronic brain syndrome (n = 14), cerebrovascular accident (n = 5), and above-the-knee amputation (n = 2). Treatment regimens included standard wound care, pressure relief and, where appropriate, culture-specific antibiotics, as well as a rehabilitation program. Home care progressively decreased the frequency of the nurse HHC and physician office visits. Resolution of the pressure ulcer varied from 6 to 32 weeks. Only two patients had progression of their wound and required hospital readmission. The billable fees included: 1) an office visit, $30.00 (medicare reimbursement, $14.00); 2) the HHC nurse visit, $159.00 (medicare reimbursement, $105.00); 3) supplies, $75.00 to $150.00/week (variable reimbursement); 4) hospitalization, $400.00 to $900.00/day; and 5) a chronic-care bed, $400.00 to $750.00/day. HHC, given a responsible support team and an involved family member, was more socially and financially acceptable than an inpatient facility. Intermittent physician visits with HHC proved safe and reliable, with 90 per cent successfully healing their wounds.


Subject(s)
Home Care Services, Hospital-Based , Hospitalization , Pressure Ulcer/therapy , Aged , Costs and Cost Analysis , Female , Home Care Services, Hospital-Based/economics , Home Nursing , Hospitalization/economics , Humans , Male , Middle Aged , Pressure Ulcer/complications , Pressure Ulcer/economics , Risk Factors
12.
Ostomy Wound Manage ; 44(3A Suppl): 78S-88S; discussion 89S, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9626001

ABSTRACT

To assess the prevalence, documentation and care of pressure ulcers, and the effect of teaching and prevention strategies in a 750-bed university hospital, one-day studies were conducted in 1993, 1995, and 1997. Data gathered was used to evaluate areas in need of improvement and find cost-effective ways to reduce the prevalence of pressure ulcers. The overall prevalence of ulcers decreased from 18 percent in 1993 to 10 percent in 1995 and 1997. The prevalence of nosocomial ulcers decreased from 14 percent in 1993 to 8 percent in 1995 and 6 percent in 1997. The number of nutritional consults increased from 54 percent in 1993 to 67 percent in 1997, and more than half of all patients tested had serum albumin levels < 3.5 mg/dL. Skin assessments upon admission were completed in the majority of patients. While ulcer documentation was less than adequate for the majority of patients in 1993 and 1997, care measures, e.g., placement of patients on specialty beds or mattresses and use of dressings that provide a moist environment, improved considerably. The results of this study indicate that system-wide educational efforts aimed at all levels of patient care providers, and multi-specialty prevention and care efforts can reduce the prevalence of pressure ulcers.


Subject(s)
Hospitals, University , Pressure Ulcer/etiology , Pressure Ulcer/prevention & control , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nursing Assessment , Nursing Audit , Nursing Staff, Hospital/education , Philadelphia , Prevalence , Quality Assurance, Health Care , Risk Factors
13.
Holist Nurs Pract ; 12(2): 38-43, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9429351

ABSTRACT

The health promotion needs of persons with schizophrenia have not been emphasized as a result of historical stigma, the effort required to stabilize symptoms, the relapsing nature of the disease, and the helplessness felt by caregivers. Family members and individuals with schizophrenia experience shame, grief, guilt, fear, and isolation, all of which render them less able to be proactive. Health promotion strategies that change attitudes, build self-esteem, increase insight into the illness, modify behavior, provide sources of income and access to medical care, and support companionship are necessary while research efforts seek a cure for this historically misunderstood illness.


Subject(s)
Health Promotion , Health Services Needs and Demand , Schizophrenia/prevention & control , Attitude to Health , Family/psychology , Humans , Prejudice , Recurrence
14.
Br J Haematol ; 97(2): 466-73, 1997 May.
Article in English | MEDLINE | ID: mdl-9163617

ABSTRACT

The outcome of allogeneic haemopoietic transplants including the rate of immune complications for patients with chronic lymphocytic leukaemia (CLL) refractory to or relapsing after chemotherapy with fludarabine was analysed. Fifteen patients with advanced CLL who received allogeneic transplantation were prospectively analysed. All patients had previously received chemotherapy with fludarabine for 3-15 courses; 12 were refractory. The median number of circulating CD4+ and CD8+ lymphocytes at the time of transplant was 0.49 x 10(9)/l and 0.23 x 10(9)/l, respectively. One patient was transplanted from a one HLA-antigen mismatched unrelated donor. Three others received a one or two antigen mismatched graft and 11 had HLA-identical sibling donors. Patients received cyclosporine or tacrolimus in addition to methotrexate or methylprednisolone for prophylaxis of acute graft-versus-host disease (aGVHD). Fourteen patients engrafted; one patient had graft failure, but recovered after therapy with intravenous immunoglobulin. 13 (87%) achieved complete remission (CR). Nine (53%) remain alive and in CR with a median follow-up of 36 (range 3-60) months. None developed visceral graft-versus-host disease. These data compared favourably to published reports in other leukaemia patients and for patients with CLL who received a comparable immunosuppressive therapy but without prior fludarabine exposure. This data indicates that allogeneic haemopoietic transplantation can induce durable remission in patients with CLL refractory to fludarabine and that it is reasonable to delay transplantation until failure of fludarabine therapy. It also suggests that prior exposure to fludarabine may decrease the incidence of severe aGVHD, possibly through its immunosuppressive effects. Further studies are warranted to evaluate this observation.


Subject(s)
Antineoplastic Agents/therapeutic use , Blood Transfusion, Autologous/methods , Bone Marrow Transplantation/methods , Graft vs Host Disease/etiology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Vidarabine/analogs & derivatives , Adult , Antineoplastic Agents/adverse effects , Blood Transfusion, Autologous/adverse effects , Bone Marrow Transplantation/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Survival Analysis , Transplantation, Homologous , Treatment Outcome , Vidarabine/adverse effects , Vidarabine/therapeutic use
15.
Clin Cancer Res ; 3(12 Pt 1): 2377-84, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9815637

ABSTRACT

Despite progress in leukemia therapy, only 20-30% of patients with acute myelogenous leukemia (AML) are cured. 1-beta-D-arabinofuranosylcytosine- and topoisomerase II-reactive drugs are the primary therapeutic agents used. The aim of this study was to evaluate the potential activity of tallimustine in leukemia. In this study, we first investigated the efficacy and toxic effects of tallimustine, a distamycin-A derivative, in a human leukemia model in severe combined immunodeficient (SCID) mice. On the basis of its dramatic activity in this preclinical study, a Phase I study of tallimustine at a starting dose of 300 microgram/m2/day for 3 days every 3-4 weeks was conducted in patients with refractory or relapsed leukemia. In SCID mice grafted with a human myelomonocytic leukemia cell line, tallimustine resulted in complete remission of disease in most mice at tolerable dosages ranging from 0.86 to 3.0 mg/kg/day for 3 days and was combined effectively and safely with a 2-day schedule of high-dose ara-C. In the Phase I study, 26 patients with refractory or relapsed leukemia were treated. The maximum tolerated dose was 900 microgram/m2/day for 3 days every 3-4 weeks. This dose was 3 times higher than the maximum tolerated dose in solid tumors and was limited by severe mucositis. Magnesium and potassium wasting were also observed, but other side effects (fatigue and gastrointestinal) were minor. Two (8%) patients with AML achieved complete remission and two achieved hematological improvement with persistent thrombocytopenia. The results of this study indicate that tallimustine has promising activity in AML. Future studies may combine tallimustine with other agents known to be active against AML, and investigate its activity in other hematological malignancies. The recommended Phase II single-agent dose of tallimustine is 750-900 microgram/m2/day for 3 days, and combination studies may start at 50-66% of this dose schedule. The SCID mouse model of human leukemia may be promising in the preclinical evaluation and selection of potential antileukemic agents.


Subject(s)
Antineoplastic Agents/adverse effects , Distamycins/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Leukemia/drug therapy , Nitrogen Mustard Compounds/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/administration & dosage , Cytarabine/therapeutic use , Diarrhea/chemically induced , Distamycins/administration & dosage , Drug Administration Schedule , Female , Humans , Injections, Intravenous , Leukemia, Myelomonocytic, Acute/drug therapy , Mice , Mice, SCID , Middle Aged , Nausea/chemically induced , Nitrogen Mustard Compounds/administration & dosage , Transplantation, Heterologous , Tumor Cells, Cultured , Vomiting/chemically induced
16.
Proc Natl Acad Sci U S A ; 93(11): 5466-71, 1996 May 28.
Article in English | MEDLINE | ID: mdl-8643598

ABSTRACT

rho-like GTP binding proteins play an essential role in regulating cell growth and actin polymerization. These molecular switches are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP. Using the interaction-trap assay to identify candidate proteins that bind the cytoplasmic region of the LAR transmembrane protein tyrosine phosphatase (PT-Pase), we isolated a cDNA encoding a 2861-amino acid protein termed Trio that contains three enzyme domains: two functional GEF domains and a protein serine/threonine kinase (PSK) domain. One of the Trio GEF domains (Trio GEF-D1) has rac-specific GEF activity, while the other Trio GEF domain (Trio GEF-D2) has rho-specific activity. The C-terminal PSK domain is adjacent to an Ig-like domain and is most similar to calcium/calmodulin-dependent kinases, such as smooth muscle myosin light chain kinase which similarly contains associated Ig-like domains. Near the N terminus, Trio has four spectrin-like repeats that may play a role in intracellular targeting. Northern blot analysis indicates that Trio has a broad tissue distribution. Trio appears to be phosphorylated only on serine residues, suggesting that Trio is not a LAR substrate, but rather that it forms a complex with LAR. As the LAR PTPase localizes to the ends of focal adhesions, we propose that LAR and the Trio GEF/PSK may orchestrate cell-matrix and cytoskeletal rearrangements necessary for cell migration.


Subject(s)
GTP-Binding Proteins/chemistry , Guanine Nucleotide Exchange Factors , Phosphoproteins/chemistry , Phosphoproteins/metabolism , Protein Serine-Threonine Kinases/chemistry , Protein Serine-Threonine Kinases/metabolism , Protein Tyrosine Phosphatases/metabolism , Amino Acid Sequence , Animals , Binding Sites , Brain/metabolism , Cell Line , Cloning, Molecular , Consensus Sequence , DNA, Complementary , GTP-Binding Proteins/metabolism , Gene Expression , Humans , Molecular Sequence Data , Myocardium/metabolism , Phosphoproteins/biosynthesis , Protein Kinases/chemistry , Protein Serine-Threonine Kinases/biosynthesis , Receptor-Like Protein Tyrosine Phosphatases, Class 4 , Receptors, Cell Surface/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Transfection , Tumor Cells, Cultured
17.
Diabetes Res Clin Pract ; 30(3): 195-203, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8861459

ABSTRACT

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.


Subject(s)
Diabetes Mellitus, Type 1/metabolism , Lipid Peroxidation/physiology , Lipoproteins, LDL/metabolism , Adult , Amidines/metabolism , Amidines/pharmacology , Cholesterol Esters/analysis , Copper/metabolism , Copper/pharmacology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/physiopathology , Glucose/chemistry , Glucose/pharmacology , Humans , Lipoproteins, LDL/chemistry , Male , Middle Aged , Osmolar Concentration , Oxidation-Reduction , Phospholipids/analysis , Reference Values , Thiobarbituric Acid Reactive Substances/metabolism , Time Factors , Triglycerides/analysis
18.
J Clin Endocrinol Metab ; 77(4): 1041-5, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8408452

ABSTRACT

Clinical evidence suggests that sex hormones affect adipose tissue metabolism and deposition. To investigate the biosynthesis and possible action of estrogen in adipose tissue, we report the use of competitive, specific polymerase chain reaction amplifications to determine levels of estrogen receptor (ER) messenger RNA (mRNA) and cytochrome P450 aromatase mRNA in adipocytes and adipose stromal cells. This extremely sensitive technique uses coamplification of a homologous animal species complementary RNA to control for differences in amplification efficiencies. The DNA amplification products are identified by Southern hybridization with species-specific radiolabeled oligonucleotide probes. Abdominal adipose tissue obtained from female patients during elective abdominoplasty was separated by collagenase digestion and centrifugation into floating adipocytes and pelleted adipose stromal cells. Our results demonstrate higher ER mRNA levels in adipocytes compared to adipose stromal cells, whereas cytochrome P450 aromatase mRNA levels are higher in adipose stromal cells compared to adipocytes. The finding of ER mRNA in adipose tissue suggests the presence of the ER in adipose tissue. In addition the inverse correlation of ER mRNA and cytochrome P450 aromatase mRNA levels in adipocytes and adipose stromal cells suggests a paracrine relationship whereby estrogen produced by adipose stromal cells affects adjacent adipocytes.


Subject(s)
Adipocytes/metabolism , Adipose Tissue/cytology , Aromatase/biosynthesis , Receptors, Estrogen/biosynthesis , Stromal Cells/metabolism , Animals , Aromatase/genetics , Base Sequence , Blotting, Northern , DNA Primers/chemistry , Female , Humans , Mice , Middle Aged , Molecular Sequence Data , Oligonucleotide Probes/chemistry , Oligonucleotides , Polymerase Chain Reaction , RNA, Messenger/analysis , Rats , Receptors, Estrogen/genetics , Transcription, Genetic
19.
J Appl Physiol (1985) ; 72(6): 2510-4, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1321113

ABSTRACT

Biomechanical unloading of the rat soleus by hindlimb unweighting is known to induce atrophy and a slow- to fast-twitch transition of skeletal muscle contractile properties, particularly in slow-twitch muscles such as the soleus. The purpose of this study was to determine whether the expression of the dihydropyridine (DHP) receptor gene is upregulated in unloaded slow-twitch soleus muscles. A rat DHP receptor cDNA was isolated by screening a random-primed cDNA lambda gt10 library from denervated rat skeletal muscle with oligonucleotide probes complementary to the coding region of the rabbit DHP receptor cDNA. Muscle mass and DHP receptor mRNA expression were assessed 1, 4, 7, 14, and 28 days after hindlimb unweighting in rats by tail suspension. Isometric twitch contraction times of soleus muscles were measured at 28 days of unweighting. Northern blot analysis showed that tissue distribution of DHP receptor mRNA was specific for skeletal muscle and expression was 200% greater in control fast-twitch extensor digitorum longus (EDL) than in control soleus muscles. A significant stimulation (80%) in receptor message of the soleus was induced as early as 24 h of unloading without changes in muscle mass. Unloading for 28 days induced marked atrophy (control = 133 +/- 3 vs. unweighted = 62.4 +/- 1.8 mg), and expression of the DHP receptor mRNA in the soleus was indistinguishable from levels normally expressed in EDL muscles. These changes in mRNA expression are in the same direction as the 37% reduction in time to peak tension and 28% decrease in half-relaxation time 28 days after unweighting. Our results suggest that muscle loading necessary for weight support modulates the expression of the DHP receptor gene in the soleus muscle.


Subject(s)
Muscles/metabolism , Receptors, Nicotinic/genetics , Animals , Base Sequence , Biomechanical Phenomena , Calcium Channels , DNA/genetics , DNA Probes , Female , Gene Expression Regulation , Molecular Sequence Data , Muscle Contraction/genetics , Muscle Contraction/physiology , Muscular Atrophy/etiology , Muscular Atrophy/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits , Rats , Rats, Inbred Strains , Sequence Homology, Nucleic Acid , Weightlessness/adverse effects
20.
Ann Clin Biochem ; 24 ( Pt 1): 22-8, 1987 Jan.
Article in English | MEDLINE | ID: mdl-3827181

ABSTRACT

Plasma calcium, serum 25 hydroxyvitamin D [25(OH)D], 1,25 dihydroxyvitamin D[1,25(OH)2D] and parathyroid hormone (PTH) have been measured in pregnant and newborn Caucasians and Asians. Calcium and 25(OH)D concentrations were lower in Caucasian than in Asian women at all four stages (three trimesters and during labour) of pregnancy. PTH concentrations were greater in Asian than in Caucasian women during the three trimesters, but not at labour, and increased in both groups through pregnancy, without a concomitant change in plasma calcium concentrations. There was a significant inverse correlation between calcium and PTH, as well as 25(OH)D and PTH, concentrations. These data demonstrate the presence of progressive 'hyperparathyroidism' during pregnancy in Caucasian and Asian women. The higher PTH concentrations in Asian women may reflect the necessity of maintaining adequate plasma calcium concentrations through PTH-induced osteolysis in the face of vitamin D deficiency. Relative hyperparathyroidism in Asians may contribute to net loss of calcium from the skeleton and osteopenia in Asian women. Calcium, 25(OH)D and 1,25(OH)2D concentrations were lower, and those of PTH higher, in Asian newborns compared with Caucasian newborns. Serum 1,25(OH)2D concentrations in the Asian newborn, though lower than respective maternal levels, were comparable with normal adult levels, indicating that 1,25(OH)2D biosynthesis is stimulated in the Asian newborn to compensate for the low serum 25(OH)D concentrations.


Subject(s)
Asian People , Calcium/blood , Parathyroid Hormone/blood , Pregnancy/blood , Vitamin D/blood , White People , Alkaline Phosphatase/blood , Calcifediol/blood , Calcitriol/blood , Female , Humans , Magnesium/blood , Phosphorus/blood , Serum Albumin/analysis
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