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Books by Enrique Battaner

La muerte ha ocupado un lugar central en la conciencia del hombre desde que ésta existe. Una y ot... more La muerte ha ocupado un lugar central en la conciencia del hombre desde que ésta existe. Una y otra vez, los arqueólogos nos muestran restos de ritos funerarios asociados a los más antiguos asentamientos humanos, lo que indica la preocupación del hombre primitivo por la muerte. Encontramos una culminación de este fenómeno en las pirámides faraónicas: todo un país trabajando en función de un monumento funerario. El hecho de desaparecer de este mundo, de la mera descomposición física del cuerpo, ha impulsado a la cultura humana en un doble sentido: Primero, la conmemoración de quien muere, el afán de que su memoria persista; segundo, buscar una escapatoria a tal destino, obviamente indeseable. La cultura egipcia, que hemos citado, buscó ambas cosas de forma insistente. La memoria del faraón Keops ha quedado indemne a lo largo de casi cuatro mil años en la forma de una inmensa pirámide de piedra, así como la de otros muchos que le sucedieron; y en cuanto a lo segundo, los egipcios perfeccionaron la técnica de embalsamamiento hasta tal punto que la ciencia actual ha conseguido aislar el ADN de la momia de Ramsés II. Platón: Su diálogo Fedón es un bellísimo tratado sobre la inmortalidad del alma. Al tiempo, la conciencia de muerte induce al hombre a pensar en la no-muerte, en la inmortalidad. En todas las culturas, vemos indefectiblemente que tal característica es atributo de los dioses. Pero cuando la conciencia humana da un paso más adelante y comienza a hacerse las preguntas clásicas: quiénes somos, de dónde venimos y a dónde

Papers by Enrique Battaner

Oncogene, 2000

The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS... more The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS-CHOP fusion gene. We previously developed a mouse model of liposarcoma by expressing FUS-CHOP in murine mesenchymal stem cells. In order to understand how FUS-CHOP can initiate liposarcoma, we have now generated transgenic mice expressing altered forms of the FUS-CHOP protein. Transgenic mice expressing high levels of CHOP, which lacks the FUS domain, do not develop any tumor despite its tumorigenicity in vitro and widespread activity of the EF1a promoter. These animals consistently show the accumulation of a glycoprotein material within the terminally dierentiated adipocytes, a characteristic ®gure of liposarcomas associated with FUS-CHOP. On the contrary, transgenic mice expressing the altered form of FUS-CHOP created by the in frame fusion of the FUS domain to the carboxy end of CHOP (CHOP-FUS) developed liposarcomas. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1a promoter. The characteristics of the liposarcomas arising in the CHOP-FUS mice were very similar to those previously observed in our FUS-CHOP transgenic mice indicating that the FUS domain is required not only for transformation but also in¯uences the phenotype of the tumor cells. These results provide evidence that the FUS domain of FUS-CHOP plays a speci®c and critical role in the pathogenesis of liposarcoma. Oncogene (2000) 19, 6015 ± 6022.

Oncogene, 2000

The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that e... more The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1a (EF1a) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-speci®c genes and a concordant block in the dierentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARg, whereas it is not expressed in embryonic ®broblasts from these animals following induction to dierentiation toward the adipocyte lineage, indicating that the in vitro system does not really re¯ect the in vivo situation and the developmental defect is downstream of PPARg expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1a promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the ®rst in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

Clinica Chimica Acta, 1983

In this paper we report the levels of the 4-nitrophenyl phosphate hydrolysing activity of the red... more In this paper we report the levels of the 4-nitrophenyl phosphate hydrolysing activity of the red blood cell membrane in 46 hypertensive patients as compared to 41 normal controls and eight secondary hypertensives. This activity has at least two components; one of them is dependent on the presence of magnesium and potassium ions, and more sensitive to sodium, ATP, heat and -SH blockers than the cation-independent activity. This component appears increased in membranes from essential hypertension patients, correlating to the clinical seriousness of the condition, while remaining at control level in the secondary hypertension patients. The cation-independent component of this activity does not differ significantly in any of the groups studied.

Life Sciences, 1985

Summar X Essential hypertension patients can be divided into two groups on the basis of the prese... more Summar X Essential hypertension patients can be divided into two groups on the basis of the presence or absence of a plasma factor able to inhibit rubidium uptake and sodium extrusion by the red blood cells. Nearly fifty percent of the patients studied present this factor. Preliminary results show that it is dialyzable, has a molecular weight around 500 daltons and cannot be extracted by chloroform.

Oncogene, 2002

Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer dev... more Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer development. The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS ± CHOP fusion gene. In the past, we generated FUS ± CHOP and CHOP transgenic mice and have shown that while FUS ± CHOP transgenic develop liposarcomas, mice expressing CHOP, which lacks the FUS domain, display essentially normal white adipose tissue (WAT) development, suggesting that the FUS domain of FUS ± CHOP plays a speci®c and critical role in the pathogenesis of liposarcoma. To test the signi®cance of FUS and CHOP domain interactions within a living mouse, we generated mice expressing the FUS domain and crossed them with CHOP-transgenic mice to generate double-transgenic FUSxCHOP animals. Here we report that expression of the FUS domain restores liposarcoma development in CHOP-transgenic mice. Our results provide genetic evidence that FUS and CHOP domains function in trans for the mutual restoration of liposarcoma. These results identify a new mechanism of tumor-associated fusion genes and might have impact beyond myxoid liposarcoma.

Physiology & Behavior, 1987

This report presents evidence of changes in the concentration of monoamine neurotransmitters and ... more This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non-mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies.

Neuroscience …, 1987

This paper describes the effects of castration and testosterone replacement on the Na+,K+-ATPase ... more This paper describes the effects of castration and testosterone replacement on the Na+,K+-ATPase activity levels of the cerebral cortex (CC), preoptic-suprachiasmatic region (POSC) and mediobasal hypothalamus (MBH) in male rats. Na+,K+-ATPase activity was estimated as the ouabain-sensitive fraction of ADP and AMP generation rate, measured by high-pressure liquid chromatography (HPLC) with UV detection, from a standard incubation mixture containing 3 mM ATP. Orchidectomy, performed 4 weeks before sacrifice, decreased ATPase activity of MBH. Testosterone propionate treatment (50 micrograms/day X 2 days) to castrated animals resulted in a 4-fold increase in enzyme activity in the POSC, an effect that might be related to the behavioral effects of androgens. None of the treatments seemed to influence the enzyme activity of the cerebral cortex.

Physiology & Behavior, 1989

We have previously shown that Na,K-ATPase activity (the enzymatic machinery for the sodium pump) ... more We have previously shown that Na,K-ATPase activity (the enzymatic machinery for the sodium pump) in brain areas such as the medial basal hypothalamus (MBH) and the preoptic-suprachiasmatic region (POSC) can be changed by experimental manipulations of gonadal function. We now report enzyme levels in brain regions as related to hormonal changes occurring during sexual behavior. Male rats were exposed to receptive females and decapitated immediately after displaying one of the following behavioral events: the start of copulatory activity, first ejaculation, and the beginning of a second copulatory series. A group of noncopulating animals were used as control. The variables measured included serum levels of LH, PRL and testosterone and Na,K-ATPase activity in MBH, POSC and parietal cerebral cortex (CC). A steady increase in enzyme activity in the POSC, but not the MBH or CC, was found in copulating animals. Serum LH levels changed in a similar fashion. A sharp increase in serum PRL levels, seemingly related to ejaculation, was also observed. These data are consistent with our previous findings on monoaminergic neurotransmission in brain regions related to male sexual behavior.

Journal of the American Society of Echocardiography, 1999

Brain research, 1987

Synaptosomal Na ÷,K ÷-transporting ATPase activity of the mediobasal hypothalamus (MBH), the medi... more Synaptosomal Na ÷,K ÷-transporting ATPase activity of the mediobasal hypothalamus (MBH), the medial preoptic-suprachiasmatic (POSC) region and cerebral cortex was measured in rats at different stages of the estrous cycle and after ovariectomy and estradiol replacement. Enzyme activity of the MBH and POSC showed cyclic changes. In both regions it increased shortly before the proestrus surge of LH. However, the two areas responded to castration and estrogen treatment in an opposite fashion. No changes were detected in enzyme activity in the cerebral cortex. These findings are consistent with previous reports on cyclic changes in electrical activity and suggest that Na ÷,K+-ATPase activity could be a useful indicator of neural activity for the study of neuroendocrine interactions.

La muerte ha ocupado un lugar central en la conciencia del hombre desde que ésta existe. Una y ot... more La muerte ha ocupado un lugar central en la conciencia del hombre desde que ésta existe. Una y otra vez, los arqueólogos nos muestran restos de ritos funerarios asociados a los más antiguos asentamientos humanos, lo que indica la preocupación del hombre primitivo por la muerte. Encontramos una culminación de este fenómeno en las pirámides faraónicas: todo un país trabajando en función de un monumento funerario. El hecho de desaparecer de este mundo, de la mera descomposición física del cuerpo, ha impulsado a la cultura humana en un doble sentido: Primero, la conmemoración de quien muere, el afán de que su memoria persista; segundo, buscar una escapatoria a tal destino, obviamente indeseable. La cultura egipcia, que hemos citado, buscó ambas cosas de forma insistente. La memoria del faraón Keops ha quedado indemne a lo largo de casi cuatro mil años en la forma de una inmensa pirámide de piedra, así como la de otros muchos que le sucedieron; y en cuanto a lo segundo, los egipcios perfeccionaron la técnica de embalsamamiento hasta tal punto que la ciencia actual ha conseguido aislar el ADN de la momia de Ramsés II. Platón: Su diálogo Fedón es un bellísimo tratado sobre la inmortalidad del alma. Al tiempo, la conciencia de muerte induce al hombre a pensar en la no-muerte, en la inmortalidad. En todas las culturas, vemos indefectiblemente que tal característica es atributo de los dioses. Pero cuando la conciencia humana da un paso más adelante y comienza a hacerse las preguntas clásicas: quiénes somos, de dónde venimos y a dónde

Oncogene, 2000

The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS... more The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS-CHOP fusion gene. We previously developed a mouse model of liposarcoma by expressing FUS-CHOP in murine mesenchymal stem cells. In order to understand how FUS-CHOP can initiate liposarcoma, we have now generated transgenic mice expressing altered forms of the FUS-CHOP protein. Transgenic mice expressing high levels of CHOP, which lacks the FUS domain, do not develop any tumor despite its tumorigenicity in vitro and widespread activity of the EF1a promoter. These animals consistently show the accumulation of a glycoprotein material within the terminally dierentiated adipocytes, a characteristic ®gure of liposarcomas associated with FUS-CHOP. On the contrary, transgenic mice expressing the altered form of FUS-CHOP created by the in frame fusion of the FUS domain to the carboxy end of CHOP (CHOP-FUS) developed liposarcomas. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1a promoter. The characteristics of the liposarcomas arising in the CHOP-FUS mice were very similar to those previously observed in our FUS-CHOP transgenic mice indicating that the FUS domain is required not only for transformation but also in¯uences the phenotype of the tumor cells. These results provide evidence that the FUS domain of FUS-CHOP plays a speci®c and critical role in the pathogenesis of liposarcoma. Oncogene (2000) 19, 6015 ± 6022.

Oncogene, 2000

The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that e... more The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1a (EF1a) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-speci®c genes and a concordant block in the dierentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARg, whereas it is not expressed in embryonic ®broblasts from these animals following induction to dierentiation toward the adipocyte lineage, indicating that the in vitro system does not really re¯ect the in vivo situation and the developmental defect is downstream of PPARg expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1a promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the ®rst in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

Clinica Chimica Acta, 1983

In this paper we report the levels of the 4-nitrophenyl phosphate hydrolysing activity of the red... more In this paper we report the levels of the 4-nitrophenyl phosphate hydrolysing activity of the red blood cell membrane in 46 hypertensive patients as compared to 41 normal controls and eight secondary hypertensives. This activity has at least two components; one of them is dependent on the presence of magnesium and potassium ions, and more sensitive to sodium, ATP, heat and -SH blockers than the cation-independent activity. This component appears increased in membranes from essential hypertension patients, correlating to the clinical seriousness of the condition, while remaining at control level in the secondary hypertension patients. The cation-independent component of this activity does not differ significantly in any of the groups studied.

Life Sciences, 1985

Summar X Essential hypertension patients can be divided into two groups on the basis of the prese... more Summar X Essential hypertension patients can be divided into two groups on the basis of the presence or absence of a plasma factor able to inhibit rubidium uptake and sodium extrusion by the red blood cells. Nearly fifty percent of the patients studied present this factor. Preliminary results show that it is dialyzable, has a molecular weight around 500 daltons and cannot be extracted by chloroform.

Oncogene, 2002

Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer dev... more Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer development. The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS ± CHOP fusion gene. In the past, we generated FUS ± CHOP and CHOP transgenic mice and have shown that while FUS ± CHOP transgenic develop liposarcomas, mice expressing CHOP, which lacks the FUS domain, display essentially normal white adipose tissue (WAT) development, suggesting that the FUS domain of FUS ± CHOP plays a speci®c and critical role in the pathogenesis of liposarcoma. To test the signi®cance of FUS and CHOP domain interactions within a living mouse, we generated mice expressing the FUS domain and crossed them with CHOP-transgenic mice to generate double-transgenic FUSxCHOP animals. Here we report that expression of the FUS domain restores liposarcoma development in CHOP-transgenic mice. Our results provide genetic evidence that FUS and CHOP domains function in trans for the mutual restoration of liposarcoma. These results identify a new mechanism of tumor-associated fusion genes and might have impact beyond myxoid liposarcoma.

Physiology & Behavior, 1987

This report presents evidence of changes in the concentration of monoamine neurotransmitters and ... more This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non-mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies.

Neuroscience …, 1987

This paper describes the effects of castration and testosterone replacement on the Na+,K+-ATPase ... more This paper describes the effects of castration and testosterone replacement on the Na+,K+-ATPase activity levels of the cerebral cortex (CC), preoptic-suprachiasmatic region (POSC) and mediobasal hypothalamus (MBH) in male rats. Na+,K+-ATPase activity was estimated as the ouabain-sensitive fraction of ADP and AMP generation rate, measured by high-pressure liquid chromatography (HPLC) with UV detection, from a standard incubation mixture containing 3 mM ATP. Orchidectomy, performed 4 weeks before sacrifice, decreased ATPase activity of MBH. Testosterone propionate treatment (50 micrograms/day X 2 days) to castrated animals resulted in a 4-fold increase in enzyme activity in the POSC, an effect that might be related to the behavioral effects of androgens. None of the treatments seemed to influence the enzyme activity of the cerebral cortex.

Physiology & Behavior, 1989

We have previously shown that Na,K-ATPase activity (the enzymatic machinery for the sodium pump) ... more We have previously shown that Na,K-ATPase activity (the enzymatic machinery for the sodium pump) in brain areas such as the medial basal hypothalamus (MBH) and the preoptic-suprachiasmatic region (POSC) can be changed by experimental manipulations of gonadal function. We now report enzyme levels in brain regions as related to hormonal changes occurring during sexual behavior. Male rats were exposed to receptive females and decapitated immediately after displaying one of the following behavioral events: the start of copulatory activity, first ejaculation, and the beginning of a second copulatory series. A group of noncopulating animals were used as control. The variables measured included serum levels of LH, PRL and testosterone and Na,K-ATPase activity in MBH, POSC and parietal cerebral cortex (CC). A steady increase in enzyme activity in the POSC, but not the MBH or CC, was found in copulating animals. Serum LH levels changed in a similar fashion. A sharp increase in serum PRL levels, seemingly related to ejaculation, was also observed. These data are consistent with our previous findings on monoaminergic neurotransmission in brain regions related to male sexual behavior.

Journal of the American Society of Echocardiography, 1999

Brain research, 1987

Synaptosomal Na ÷,K ÷-transporting ATPase activity of the mediobasal hypothalamus (MBH), the medi... more Synaptosomal Na ÷,K ÷-transporting ATPase activity of the mediobasal hypothalamus (MBH), the medial preoptic-suprachiasmatic (POSC) region and cerebral cortex was measured in rats at different stages of the estrous cycle and after ovariectomy and estradiol replacement. Enzyme activity of the MBH and POSC showed cyclic changes. In both regions it increased shortly before the proestrus surge of LH. However, the two areas responded to castration and estrogen treatment in an opposite fashion. No changes were detected in enzyme activity in the cerebral cortex. These findings are consistent with previous reports on cyclic changes in electrical activity and suggest that Na ÷,K+-ATPase activity could be a useful indicator of neural activity for the study of neuroendocrine interactions.