RESUMEN
PURPOSE: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin. METHODS: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls. RESULTS: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]). CONCLUSION: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.
Asunto(s)
Proteína BRCA2 , Neoplasias de la Mama Masculina , Neoplasias de la Mama , Judíos , Proteína BRCA2/genética , Neoplasias de la Mama/etnología , Neoplasias de la Mama/genética , Neoplasias de la Mama Masculina/etnología , Neoplasias de la Mama Masculina/genética , Etiopía/epidemiología , Femenino , Efecto Fundador , Predisposición Genética a la Enfermedad , Humanos , Judíos/genética , Masculino , Estudios RetrospectivosRESUMEN
Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.
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Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Reparación de la Incompatibilidad de ADN/genética , Etiopía , Mutación de Línea Germinal , Humanos , Judíos/genética , Persona de Mediana Edad , Proteína 2 Homóloga a MutS/genética , Adulto JovenRESUMEN
Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remain poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate a globally consistent, continuous index of forest condition as determined by the degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) has high landscape-level integrity (mostly found in Canada, Russia, the Amazon, Central Africa, and New Guinea) and only 27% of this area is found in nationally designated protected areas. Of the forest inside protected areas, only 56% has high landscape-level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.
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Biodiversidad , Conservación de los Recursos Naturales/estadística & datos numéricos , Política Ambiental , Bosques , África Central , Canadá , Cambio Climático , Conservación de los Recursos Naturales/legislación & jurisprudencia , Nueva Guinea , Federación de RusiaRESUMEN
We have shown previously that the regulatory subunit (RII) of a type II cAMP-dependent protein kinase is an integral component of the mammalian sperm flagellum (Horowitz, J.A., H. Toeg, and G.A. Orr. 1984. J. Biol. Chem. 259:832-838; Horowitz, J.A., W. Wasco, M. Leiser, and G.A. Orr. 1988. J. Biol. Chem. 263:2098-2104). The subcellular localization of this flagellum-associated RII in bovine caudal epididymal sperm was analyzed at electron microscope resolution with gold-conjugated secondary antibody labeling techniques using anti-RII monoclonal antibodies. By immunoblot analysis, the flagellum-associated RII was shown to interact with mAb 622 which cross reacts with both neural and nonneural isoforms of RII. In contrast, a neural specific monoclonal antibody (mAb 526) failed to interact with flagellar RII. In the midpiece of the demembranated sperm tail, gold label after mAb 622 incubation was primarily associated with the outer mitochondrial membrane. Although almost all specific labeling in the midpiece can be assigned to the mitochondria, in the principal piece, there is some labeling of the fibrous sheath. Labeling of the outer dense fibers and the axoneme was sparse. Specific labeling was virtually absent in the sperm head. Sections of sperm tails incubated in the absence of primary antisera or with mAb 526 showed little labeling. A beta-tubulin monoclonal antibody localized only to the 9 + 2 axoneme. These results raise the possibility that a type II cAMP-dependent protein kinase located at the outer mitochondrial membrane plays a role in the direct cAMP stimulation of mitochondrial respiration during sperm activation.
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Flagelos/análisis , Proteínas Quinasas/análisis , Adenosina Trifosfatasas/fisiología , Animales , Anticuerpos Monoclonales , Especificidad de Anticuerpos , Electroforesis en Gel de Poliacrilamida , Immunoblotting , Inmunohistoquímica , Membranas Intracelulares/análisis , Masculino , Mitocondrias/análisis , Espermatozoides/citologíaRESUMEN
In four patients with hypercholesterolemia (type II hyperlipoproteinemia) and xanthomatosis the decay of serum cholesterol specific activity was followed for 53-63 wk after pulse labeling. Specific activity of biopsied xanthoma cholesterol was measured four times in the course of the study. The xanthoma specific activity curve crossed and thereafter remained above the serum specific activity curve. The average ratio of xanthoma to serum specific activity was 4.7 at the end of the study. The final half-time of the xanthoma decay curves was significantly greater (average: 200 days) than the slowest half-time of serum specific activity decay (average: 93 days). The data were analyzed by input-output analysis and yielded the following results. The average value for the total input rate of body cholesterol (I(T)) (sum of dietary and biosynthesized cholesterol) was 1.29 g/day. The average size of the rapidly miscible pool of cholesterol (M(a)) was 55.7 g. and of the total exchangeable body mass of cholesterol (M) 116.5 g. The average value of M - M(a) (remaining exchangeable mass of cholesterol) was 60.8 g. The derived values for exchangeable masses of cholesterol, in the present patients with marked hypercholesterolemia, were significantly larger than in a group of patients with normal serum lipids in previous studies. One of the four patients died of a sudden acute myocardial infarction 53 wk after pulse labeling. Specific activity of aortic wall and atheroma cholesterol was 3.12 times that of serum. The ratio was close to 2 for adipose tissue and spleen, and was slightly above 1 or was close to unity in most other organs studied, with the exception of brain which showed a ratio of 0.19.
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Colesterol/metabolismo , Hipercolesterolemia/metabolismo , Xantomatosis/metabolismo , Adolescente , Autorradiografía , Peso Corporal , Isótopos de Carbono , Colesterol/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/metabolismo , Femenino , Humanos , Hipercolesterolemia/sangre , Cinética , Masculino , Persona de Mediana Edad , Factores de Tiempo , Triglicéridos/sangre , Xantomatosis/sangreRESUMEN
We have shown previously that the immunoglobulin heavy-chain enhancer acts as a repressor of gene transcription in hybrids between immunoglobulin-producing myelomas and a T-lymphoma line. We have now mapped this repressive activity to a 51-bp enhancer subfragment which contains the octamer and mu E4 protein-binding motifs. Even a single copy of this subfragment will repress gene expression in hybrid cells. Mutational analyses of the repressor fragment suggest that in non-B cells, a strong transcriptional repressor(s) functions through the same motifs important for gene activation in B cells. Changes in chromatin structure that accompany reporter gene repression suggest a general mechanism for prohibiting immunoglobulin heavy-chain locus activation in inappropriate cell types.
Asunto(s)
Elementos de Facilitación Genéticos , Genes de Inmunoglobulinas , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas mu de Inmunoglobulina/genética , Linfoma de Células T/inmunología , Mieloma Múltiple/inmunología , Animales , Secuencia de Bases , Clonación Molecular , Desoxirribonucleasa I , Escherichia coli/enzimología , Escherichia coli/genética , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células Híbridas , Intrones , Linfoma de Células T/genética , Ratones , Datos de Secuencia Molecular , Mieloma Múltiple/genética , Pentosiltransferasa/genética , Proteínas Recombinantes de Fusión/metabolismo , Mapeo Restrictivo , Activación Transcripcional , Transfección , Células Tumorales CultivadasRESUMEN
At Naval Base Point Loma in San Diego, California, a canyon had been filled with construction debris and automotive scrap residue (ASR), the latter of which included lead acid batteries. A magnetic survey and induced potential (IP)/DC resistivity survey showed the presence of anomalies at the western end of the site where historic records indicated that the ASR had been placed. Lead concentration depth profiles were obtained in situ and in real time at the site using a direct push fiber-optic laser-induced breakdown spectroscopy (FO-LIBS) sensor probe. Lead, along with strontium and titanium, was detected at depths of 7 to 8 m bgs. These results provided confirmation that the magnetic/IP anomalies at the site are due to ASR.
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Automóviles , Monitoreo del Ambiente/instrumentación , Tecnología de Fibra Óptica/instrumentación , Residuos Industriales/análisis , Rayos Láser , Plomo/análisis , Análisis Espectral/instrumentación , California , Monitoreo del Ambiente/métodos , Contaminación Ambiental/análisis , Diseño de Equipo , Análisis de Falla de Equipo , Fibras Ópticas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , TransductoresRESUMEN
The interaction of cysteamine (CY), L-cysteine methyl ester (CYSM), and L-cysteine ethyl ester (CYSE) with nitrate, sulfate, perchlorate, dihydrogen phosphate, and chloride ions was investigated using surface enhanced Raman spectroscopy (SERS). CYSM and CYSE are chemical derivatives of CY. These thiols have a quaternary ammonium group to attract the anions to the SERS surface. Dihydrogen phosphate did not interact with these cationic thiols. The CY interaction with perchlorate, nitrate, and sulfate is stronger than the interaction with chloride. However, replacing a hydrogen on the carbon adjacent to the quaternary ammonium group with either a methyl or ethyl ester group results in stronger complexation with chloride ion than with either sulfate or nitrate ion. In the case of CYSM, the chloride interaction is five times stronger than the interaction with perchlorate. Molecular modeling indicates that the high selectivity of CYSM/CYSE for chloride is due to hydrogen bonding between the chloride ion and the hydrogen of the CH3 moeities of adjacent ester groups.
Asunto(s)
Cloruros/metabolismo , Cisteína/análogos & derivados , Cisteína/metabolismo , Cloruros/química , Simulación por Computador , Cisteamina/química , Cisteamina/metabolismo , Cisteína/química , Electroquímica , Enlace de Hidrógeno , Modelos Moleculares , Plata/química , Plata/metabolismo , Espectrometría RamanRESUMEN
The mechanisms underlying the effects of recombinant human growth hormone (rhGH) on vitamin D, mineral, and bone metabolism are not known. We examined whether these effects are mediated by parathyroid hormone (PTH) by measuring renal phosphorus (P) and calcium (Ca) handling, serum calcitriol, and markers of bone turnover for 24 h before and 72 h after an infusion of hPTH(1-34) in eight healthy postmenopausal women at baseline and following short-term (1 week) and sustained (5 weeks) rhGH treatment. On short-term rhGH, serum phosphorus and basal TmP/GFR were unaffected, but the fall in TmP/GFR after hPTH infusion was exaggerated (integrated response: -99.2 +/- 22.3 versus -144.1 +/- 15.0 minute-mg/dl, P = 0.0021). Basal calcitriol levels rose from 115 +/- 17 to 163 +/- 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH. The basal Ca excretion index (CEI) rose from 0.054 +/- 0.005 to 0.073 +/- 0.007 mM (P = 0.0095), but markers of bone turnover were unaffected. With sustained rhGH treatment, serum P (1.47 +/- 0.05 mM), basal TmP/GFR (4.29 +/- 0.24 mg/dl), and basal CEI (0.067 +/- 0.005 mM) were elevated compared with control values, and the PTH-induced lowering of TmP/GFR was again enhanced (-158.7 +/- 22.8 minute-mg/dl, P = 0.0021). Basal calcitriol concentrations returned to control levels (108 +/- 10 pM), but the calcitriol response to hPTH remained unchanged. Markers of bone remodeling were elevated with sustained rhGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Remodelación Ósea/efectos de los fármacos , Calcitriol/sangre , Calcio/metabolismo , Hormona del Crecimiento/farmacología , Hormona Paratiroidea/farmacología , Fragmentos de Péptidos/farmacología , Fósforo/metabolismo , Adenilil Ciclasas/metabolismo , Anciano , Biomarcadores/sangre , Activación Enzimática/efectos de los fármacos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Persona de Mediana Edad , Hormona Paratiroidea/efectos adversos , Hormona Paratiroidea/metabolismo , Fragmentos de Péptidos/efectos adversos , Fragmentos de Péptidos/metabolismo , Posmenopausia/metabolismo , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Teriparatido , Factores de TiempoRESUMEN
The pathways of biosynthesis of the estrogens from C19 steroids has been examined by in vitro kinetic experiments using human placental microsomes and two precursors, each labeled with a different radioisotope. The results indicate that under the conditions employed, androstenedione is an obligatory intermediate in the conversion of 3 beta-hydroxy-5-androsten-17-one (dehydroisoandrosterone) or its sulfate, dehydroisoandrosterone sulfate, into estrone and estradiol. The same result was obtained when the microsomal fraction was replaced by either a 1000 x g supernatant preparation from human placenta or a homogenate of placental mitochondria. If alternative pathways involving C19-hydroxylated derivatives of dehydroisoandrosterone or its sulfate exist, they appear to be of minor quantitative significance.
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Deshidroepiandrosterona/metabolismo , Estrógenos/biosíntesis , Microsomas/metabolismo , Placenta/metabolismo , Androstenodiona/metabolismo , Radioisótopos de Carbono , Femenino , Humanos , Marcaje Isotópico , Cinética , Embarazo , TritioRESUMEN
Homogenates obtained from bovine corpora luteal tissue were found to catalyze the synthesis of 3 beta-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) from progesterone but not from pregnenolone. The major metabolites of progesterone included allopregnanolone, 5 alpha-pregnane-3,20-dione, and fatty acid esters of allopregnanolone. Incubation with labeled pregnenolone resulted in the formation of pregnenolone esters; however, neither allopregnanolone nor esterified derivatives of it were detected. The esterifying enzyme(s) leading to the formation of allopregnanolone esters was associated primarily with the microsome-enriched subcellular fraction and was stimulated by the addition of ATP and coenzyme A. With these added cofactors, the pH optimum was 6.0-6.5. The rate of steroid ester formation was enhanced by the addition to the homogenate fraction of oleic acid, which was incorporated into the steroid ester fraction. Thus, enzymatic activity, with characteristics similar to either cholesteryl ester hydrolase (EC 3.1.1.13) or acyl cholesterol acyltransferase (EC 2.3.1.26), catalyzed the esterification of allopregnanolone. The data suggest that the allopregnanolone esters found in vivo are derived from progesterone rather than from pregnenolone.
Asunto(s)
Cuerpo Lúteo/metabolismo , Ácidos Grasos/metabolismo , Pregnanodionas/metabolismo , Pregnanos/metabolismo , Pregnanolona/metabolismo , Progesterona/metabolismo , 5-alfa-Dihidroprogesterona , Animales , Bovinos , Cromatografía Líquida de Alta Presión , Femenino , Concentración de Iones de Hidrógeno , Modelos Químicos , Fracciones Subcelulares/metabolismoRESUMEN
The loss of lean body mass accompanying acquired immunodeficiency syndrome (AIDS)-associated cachexia is refractory to current modes of therapy. GH and insulin-like growth factor-I (IGF-I) stimulate protein accretion, but resistance to GH action has been reported in malnutrition and infection. We hypothesized that GH resistance occurs in AIDS-associated cachexia, but that treatment with IGF-I would be anabolic. A single injection of GH produced a smaller increase in circulating IGF-I in 21 patients with AIDS compared to that in 23 age-matched controls (141 +/- 15 vs. 194 +/- 15 micrograms/L; P < 0.02), indicating partial GH resistance. Ten subjects received either low or high dose iv recombinant IGF-I 12 h daily for 10 days. Cumulative nitrogen retention was positive for both dosage groups (low dose, 15.42 +/- 6.37 g; high dose, 3.62 +/- 4.15 g), but a significant increase in daily nitrogen retention occurred only in the low dose group on days 2, 4, 5, 6, and 7. Nitrogen balance and protein turnover (estimated by [13C]leucine and [15N] glycine kinetics) during the final 3 days of treatment were unchanged compared to baseline values, confirming the transient nature of the anabolic response. Repeated administration of IGF-I decreased IGF-binding protein-3 levels, producing lower intrainfusion levels of IGF-I and limiting its therapeutic efficacy. The basal metabolic rate increased with high dose IGF-I and may have contributed to the lack of anabolic effect. We conclude that partial GH resistance occurs in AIDS-associated cachexia. Treatment with low dose recombinant IGF-I produces significant, but transient, nitrogen retention. Alternate routes of IGF-I administration or coadministration with GH may prevent attenuation of IGF-I action.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Caquexia/complicaciones , Caquexia/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/metabolismo , Adulto , Antropometría , Índice de Masa Corporal , Antígenos CD4/análisis , Caquexia/metabolismo , Proteínas Portadoras/sangre , Relación Dosis-Respuesta a Droga , Metabolismo Energético/fisiología , Glicina/metabolismo , Hormona del Crecimiento/farmacología , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/efectos adversos , Factor I del Crecimiento Similar a la Insulina/análisis , Leucina/metabolismo , Linfocitos/inmunología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Nitrógeno/metabolismo , Nitrógeno/orina , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/sangre , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Although hypopituitarism is a known complication of head injury, it may be underrecognized due to its subtle clinical manifestations. The nonspecific symptoms may be masked by and may contribute to the physical and psychological sequelae of brain trauma. This study examines the prevalence of neuroendocrine abnormalities in patients rehabilitating from traumatic brain injury. Seventy adults (mean age, 31.5 +/- 1.1 yr; range, 18--58; 46 men and 24 women) with traumatic brain injury an average of 49 +/- 8 months before the study (median, 13 months) underwent a series of standard endocrine tests, including serum levels of TSH, free T(4), insulin-like growth factor I, PRL, testosterone (males), and cosyntropin stimulation. Abnormal results of these tests were followed by dynamic tests of gonadotropin, TSH, and GH secretion. Glucagon stimulation testing in 48 subjects revealed GH deficiency (peak, <3 microg/L) in 14.6%. Free T(4) (n = 6; 8.6%), TSH (n = 7; 10%), or both (n = 2; 2.9%) were low in 21.7%, whereas 87% had both TSH and free T(4) below the midnormal level. Basal morning cortisol was below normal in 45.7% of subjects, whereas cosyntropin-stimulated levels were insufficient (peak, <500 nmol/L) in 7.1%. Hypogonadism and hyperprolactinemia were uncommon. In summary, pituitary hormone deficiencies were identified in a substantial proportion of patients with previous brain injury. GH deficiency, found in 15% by glucagon stimulation testing, may compound the physical and psychological complications of traumatic brain injury and interfere with rehabilitation.
Asunto(s)
Lesiones Encefálicas/complicaciones , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/etiología , Adulto , Lesiones Encefálicas/metabolismo , Enfermedades del Sistema Endocrino/metabolismo , Femenino , Hormona de Crecimiento Humana/deficiencia , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/metabolismo , Prevalencia , Prolactina/sangre , Texas , Tironinas/deficiencia , Tirotropina/deficienciaRESUMEN
To examine the effects of repeated administration of recombinant human insulin-like growth factor-I (rhIGF-I) on IGF-I levels, free IGF-I pharmacokinetics, glycemic response, and IGF-binding proteins (IGFBP), we administered rhIGF-I (0.03 mg/kg iv bolus) to 12 healthy males each morning for 5 consecutive days. Serum was collected over 24 h on days 1 and 5 for measurement of total and free IGF-I, glucose, insulin, and IGFBP. Total IGF-I was measured by RIA after acid/ethanol extraction. Free IGF-I was separated from binding protein-complexed IGF-I using size exclusion high performance liquid chromatography before measurement by RIA. IGFBP were quantitated by optical densitometry of Western ligand blots. Total IGF-I increased significantly from 0-24 h after administration on day 1 (mean +/- SD, micrograms/L: 120 +/- 44 to 166 +/- 51, P = 0.0002) but did not increase significantly from 24 h on day 1 to 0 h on day 5 (166 +/- 51 to 178 +/- 62) or from 0-24 h on day 5 (178 +/- 62 to 209 +/- 89). The area under the total IGF-I concentration curve was greater on day 5 than day 1 (311 +/- 99 min.g/L vs. 249 +/- 77, P = 0.0001). There were no significant differences in free IGF-I concentration or pharmacokinetic parameters or in the degree or timing of hypoglycemia between days 1 and 5. Plasma insulin levels decreased significantly following rhIGF-I administration (day 1 baseline: 53 +/- 11 pmol/L, nadir: 18 +/- 6 pmol/L at 30 min, P = 0.003); day 5 baseline: 47 +/- 15 pmol/L, nadir: 16 +/- 8 pmol/L at 30 min, P = 0.0003. Western ligand blotting revealed the transient appearance of a 30-kilodalton band which migrates in a manner similar to IGFBP-1. This band was undetectable at baseline, peaked between 150 and 210 min after rhIGF-I administration, and diminished by 480-600 min. The response was similar on days 1 and 5. There were no substantial changes in the serum levels of any other IGFBP. In summary, repeated iv bolus administration of rhIGF-I increased the level of total circulating IGF-I without changing free IGF-I disposition or glycemic response. A 30-kilodalton IGFBP band, most likely IGFBP-1, appeared transiently following rhIGF-I administration, probably as a result of suppression of insulin levels. IGFBP-2, -3, and -4 were unaffected.
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Glucemia/análisis , Proteínas Portadoras/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/farmacología , Adulto , Western Blotting , Proteínas Portadoras/sangre , Humanos , Hipoglucemia/sangre , Insulina/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/farmacocinética , Masculino , Proteínas Recombinantes/farmacología , Somatomedinas/efectos de los fármacosRESUMEN
Eight patients with chronic anorexia nervosa were treated by the authors with a paradoxical approach. At follow-up 2-4 years later four of the patients had maintained a normal weight (within 15% of average weight), and only one patient was at a very low weight. The authors found this encouraging but caution that this technique does not address the individual's personality difficulties, for it did not appear to have improved the patients' social and sexual functioning. They believe, however, that paradoxical intention is worthy of further study in treating chronic anorexia nervosa.
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Anorexia Nerviosa/rehabilitación , Terapia Conductista/métodos , Adulto , Anorexia Nerviosa/psicología , Peso Corporal , Enfermedad Crónica , Femenino , Humanos , Masculino , Pronóstico , Intento de Suicidio/psicologíaRESUMEN
Many transplant teams are reluctant to accept kidneys preserved with intracellular electrolyte flushing followed by simple cold storage when preservation time exceeds 24 hr. This study from one center is a comparison of 63 primary cadaver kidney grafts preserved with Collins 2 solution flush followed by cold storage for 9 to 23 1/2 hr to 42 primary cadaver kidney grafts preserved by the same method for 24 to 44 1/2 hr. Kidneys cold-stored for over 24 hr had a significantly increased requirement for dialysis in the first week following transplantation (55% versus 30%). One-month serum creatinine nadirs and actuarial graft survivals were not significantly different. Cadaver donor methylprednisolone (30 to 60 mg/kg) 2 to 9 hr prior to kidney removal reduced the requirement for first-week hemodialysis in the kidneys cold-stored for over 24 hr (23% versus 69%, P under 0.05). A human kidney preserved by the same method and cold-stored for 61 hr was successfully transplanted into a 38-year-old myelodysplastic. Satisfactory human kidney preservation can occur with intracellular electrolyte flush solutions followed by cold storage for over 24 hr when the warm ischemia time is very short.
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Frío , Electrólitos/uso terapéutico , Trasplante de Riñón , Preservación de Órganos/métodos , Conservación de Tejido/métodos , Supervivencia de Injerto , Humanos , Perfusión , Factores de TiempoRESUMEN
The anabolic functions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in cartilage and bone metabolism are important in the normal physiology of these tissues. The effects of chronic elevation of GH and IGF-I levels on bony structures produce the typical physical changes associated with acromegaly, whereas the effects on cartilage result in arthropathy, which is usually degenerative. This article presents an overview of the physiologic roles of GH and IGF-I in cartilage and bone metabolism, the clinical features of the degenerative arthropathy and other rheumatologic syndromes associated with acromegaly, effects of acromegaly on bone and mineral metabolism, and an unusual bone disease that is occasionally associated with acromegaly, the McCune-Albright syndrome.
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Acromegalia/complicaciones , Huesos , Tejido Conectivo , Acromegalia/patología , Acromegalia/fisiopatología , Enfermedades Óseas/etiología , Enfermedades Óseas/patología , Enfermedades Óseas/fisiopatología , Huesos/patología , Huesos/fisiopatología , Cartílago/patología , Cartílago/fisiopatología , Tejido Conectivo/patología , Tejido Conectivo/fisiopatología , Hormona del Crecimiento/fisiología , Humanos , Factor I del Crecimiento Similar a la Insulina/fisiología , Artropatías/etiología , Artropatías/patología , Artropatías/fisiopatología , Artropatías/terapiaRESUMEN
The effect of the combined administration of pindolol (10 or 20 mg daily) and hydrochlorothiazide (50 mg daily) on the serum lipid and lipoprotein levels of 34 hypertensive patients was investigated for 6 to 18.5 months (mean 13.3). Placebo control data were compared with the results obtained during treatment periods in each patient by paired t tests. Mean levels of high-density lipoprotein cholesterol increased by 17% (p less than 0.01), low-density lipoprotein cholesterol decreased by 4% (p less than 0.01) and the high-density lipoprotein: low-density lipoprotein cholesterol ratio increased by 28% (p less than 0.01). Total serum cholesterol, serum triglycerides and very low-density lipoprotein cholesterol showed no statistically significant changes from control values. These findings suggest that the long-term administration of this beta blocker combined with a diuretic results in serum lipid changes considered beneficial in the evaluation of risk factors for coronary artery disease.
Asunto(s)
Hidroclorotiazida/administración & dosificación , Hipertensión/sangre , Lípidos/sangre , Pindolol/administración & dosificación , Adulto , Anciano , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Lipoproteína Lipasa/análisis , Masculino , Persona de Mediana Edad , Fosfatidilcolina-Esterol O-Aciltransferasa/análisis , Triglicéridos/sangreRESUMEN
The effect of isradipine versus hydrochlorothiazide on the lipid profile of 44 hypertensive patients was investigated in a double-blind, randomized, 2-center trial. Lipid profiles included total cholesterol, serum triglycerides, high density lipoprotein (HDL) cholesterol, HDL subclasses, (HDL2 and HDL3), low density lipoprotein cholesterol, very low density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B. Isradipine had no effect on the lipid profile in short- (4 and 10 week) or long-term (52 week) studies. Hydrochlorothiazide increased serum triglycerides in 11 of 13 patients by a mean of 8% for the group (p less than 0.05) in long-term (52 week) studies, and total cholesterol by a mean of 9 and 16%, respectively (p less than 0.01) in 2 of 13 patients, with no difference in other lipid or lipoprotein parameters in short- or long-term studies.