Abstract: Administration of leptin affects food intake and body weight in animals and humans by a mechanism involving actions on specific regions of the hypothalamus. CIS-1, SOCS-1, SOCS-2 and SOCS-3 genes were investigated for their ability to antagonize leptin action. In mammalian cell lines, SOCS-3 completely blocked leptin induced signal- transduction, whereas CIS, SOCS-1 and SOC-2 were without effect. SOCS-3 is a major target of leptin action in leptin responsive cells in the hypothalamus, and SOCS-3 is a potent inhibitor of leptin signaling. Increased SOCS-3 activity in leptin-responsive neurons is a potential mechanism for the leptin resistance observed in syndromes of obesity, affective mood disorders and reproductive disorders.

Abstract: Deletion of the rsk2 gene in mice results in reduced body weight, reduced body fat and reduced sensitivity to diet-induced weight gain, as well as lower levels of leptin in the serum of rsk2 deficient mice and lower levels of oxygen consumption, as compared to wild type littermates. Thus, altering RSK2 activity provides a means for modulating RSK2-mediated signaling and therefore modulating the above described physiological parameters. The present invention encompasses methods and compositions for altering, or modulating in a mammal, body weight, fat content, leptin levels by altering, or modulating, RSK2 activity. Specifically encompassed in the present invention are methods and compositions to alter activity of the RSK2. The present invention is drawn to a model for the study of Coffin-Lowry syndrome as well as an in vivo model to screen and test therapeutic agents for the treatment of Coffin-Lowry syndrome.

Abstract: Methods and compositions for altering, or modulating CNTF activity by altering or modulating cytokine inhibitor activity are provided. Specifically encompassed are methods and compositions to alter activity of cytokine inhibitors such as SOCS-1, -2, and -3. SOCS-3 expression is rapidly induced by CNTF treatment in regions of the hypothalamus that are known to be involved in the regulation of body weight. As described herein, a SOCS-3-mediated CNTF cell-signaling inhibitory pathway exists, suggesting that SOCS-3 is a negative regulator of CNTF signal-transduction in the brain. Since CNTF treatment of animals suppresses appetite and induces weight loss, inhibition of SOCS-3 expression or activity is a potential target for the development of drugs aimed at improving CNTF sensitivity or prolonging CNTF activity in a mammal and inducing weight loss. Thus, altering SOCS-3 activity provides a means for modulating CNTF-induced cell signaling and therefore modulating bodyweight.

Abstract: Methods of treating an affective disorder in an individual are disclosed. Affective disorders include major depression, melancholic and atypical subtypes, and dysthymia.

Abstract: Methods of treating an affective disorder in an individual are disclosed. Affective disorders include major depression, melancholic and atypical subtypes, and dysthymia.

Abstract: A method of chronic modification of cell barrier properties by exposing a cell to a modification-effective amount of IGF-I for at least about 7 days wherein the modification effective amount is between about 50 .mu.g/kg and less than about 500 .mu.g/kg is disclosed. Further disclosed is a method of chronic amelioration or reversal of insulin resistance as well as a method of diagnosing and screening for rhIGF-I sensitive cell barrier properties.

Abstract: A method of chronic modification of cell barrier properties by exposing a cell to a modification-effective amount of IGF-I for at least about 7 days wherein the modification effective amount is between about 50 .mu.g/kg and less than about 500 .mu.g/kg is disclosed. Further disclosed is a method of chronic amelioration or reversal of insulin resistance as well as a method of diagnosing and screening for rhIGF-I sensitive cell barrier properties.

Abstract: A method of chronic modification of cell barrier properties by exposing a cell to a modification-effective amount of IGF-I for at least about 7 days wherein the modification effective amount is between about 50 .mu.g/kg and less than about 500 .mu.g/kg is disclosed. Further disclosed is a method of chronic amelioration or reversal of insulin resistance as well as a method of diagnosing and screening for rhIGF-I sensitive cell barrier properties.

Abstract: A method of chronic modification of cell barrier properties by exposing a cell to a modification-effective amount of IGF-I for at least about 7 days wherein the modification effective amount is between about 50 .mu.g/kg and less than about 500 .mu.g/kg is disclosed. Further disclosed is a method of chronic amelioration or reversal of insulin resistance as well as a method of diagnosing and screening for rhIGF-I sensitive cell barrier properties.

Abstract: The invention provides a recombinant purified human protein in substantial quantities which has both adipsin and complement D activity. The invention also provides materials and methods to produce the protein. In addition, antibodies immunoreactive with this protein are useful to diagnose metabolic defects attributable to adipsin deficiency or complement D deficiency. The protein can be used to treat obesity caused by adipsin deficiency or to treat subjects for infection.

Abstract: Compositions and methods useful for the prevention or treatment of a human or animal disorder or for the regulation of the human or animal physiological condition are provided. The compositions used comprise, in admixture, a biologically-effective amount of a drug specific for the disorder or condition and a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, which is capable of increasing drug permeability of the human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of the surface to the drug.

Abstract: Compositions and methods useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition are provided. The compositions used comprise, in admixture, a biologically-effective amount of a drug specific for the disorder or condition and a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, which is capable of increasing drug permeability of the human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of the surface to the drug.

Abstract: A composition useful for the treatment of an animal suffering from a predetermined medical disorder including, in admixture, a medically effective amount of a drug, other than an antibiotic, effective against the medical disorder, and a biocompatible, water-soluble, amphiphilic steroid, other than a bile salt, which is capable of increasing the permeability to the drug of a surface of the animal across which the drug is to be administered, in an amount effective to increase the permeability of the surface to the drug.