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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The physicochemical properties of water enable it to act as a solvent for electrolytes, and to influence the molecular configuration and hence the function--enzymatic in particular--of polypeptide chains in biological systems. The association of water with electrolytes determines the osmotic regulation of cell volume and allows the establishment of the transmembrane ion concentration gradients that underlie nerve excitation and impulse conduction. Fluid in the central nervous system is distributed in the intracellular and extracellular spaces (ICS, ECS) of the brain parenchyma, the cerebrospinal fluid, and the vascular compartment--the brain capillaries and small arteries and veins. Regulated exchange of fluid between these various compartments occurs at the blood-brain barrier (BBB), and at the ventricular ependyma and choroid plexus, and, on the brain surface, at the pia mater. The normal BBB is relatively permeable to water, but considerably less so to ions, including the principal electrolytes Brain fluid regulation takes place within the context of systemic fluid volume control, which depends on the mutual interaction of osmo-, volume-, and pressure-receptors in the hypothalamus, heart and kidney, hormones such as vasopressin, renin-angiotensin, aldosterone, atriopeptins, and digitalis-like immunoreactive substance, and their respective sites of action. Evidence for specific transport capabilities of the cerebral capillary endothelium, for example high Na+K(+)-ATPase activity and the presence at the abluminal surface of a Na(+)--H+ antiporter, suggests that cerebral microvessels play a more active part in brain volume regulation and ion homoeostasis than do capillaries in other vascular beds. The normal brain ECS amounts to 12-19% of brain volume, and is markedly reduced in anoxia, ischaemia, metabolic poisoning, spreading depression, and conventional procedures for histological fixation. The asymmetrical distributions of Na+ K+ and Ca2+ between ICS and ECS underlie the roles of these cations in nerve excitation and conduction, and in signal transduction. The relatively large volume of the CSF, and extensive diffusional exchange of many substances between brain ECS and CSF, augment the ion-homeostasing capacity of the ECS. The choroid plexus, in addition to secreting CSF principally by biochemical mechanisms (there is an additional small component from the extracellular fluid), actively transports some substances from the blood (e.g. nucleotides and ascorbic acid), and actively removes others from the CSF. In contrast with CSF secretion, CSF reabsorption is principally a biomechanical process, passively dependent on the CSF-dural sinus pressure gradient. Pathological increases in intracranial water content imply development of an intracranial mass lesion. The additional water may be distributed diffusely within the brain parenchyma as brain oedema, as a cyst, or as increase in ventricular volume due to hydrocephalus. Brain oedema is classified on the basis of pathophysiology into four categories, vasogenic, cytotoxic, osmotic and hydrostatic. The clinical conditions in which brain oedema presents the greatest problems are tumour, ischaemia, and head injury. Peritumoural oedema is predominantly vasogenic and related to BBB dysfunction. Ischaemic oedema is initially cytotoxic, with a shift of Na+ and CI- ions from ECS to ICS, followed by osmotically obliged water, this shift can be detected by diffusion-weighted MRI. Later in the evolution of an ischaemic lesion the oedema becomes vasogenic, with disruption of the BBB. Recent imaging studies in patients with head injury suggest that the development of traumatic brain oedema may follow a biphasic time course similar to that of ischaemic oedema. Hydrocephalus is associated in the great majority of cases with an obstruction to the circulation or drainage of CSF, or, occasionally, with overproduction of CSF by a choroid plexus papilloma. In either case, the consequence is a ris
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PMID:The normal and pathological physiology of brain water. 907 71

Atomic force microscopy has been used to characterize gap junctions isolated from the hepatopancreas of Nephrops norvegicus. The major polypeptide of these gap junctions is ductin, a highly conserved 16- to 18-kDa protein. The hydrated gap junctions, imaged in phosphate-buffered saline, appeared as membrane plaques with a thickness of 14 nm, consistent with their being a pair of apposing membranes. The upper membrane was removed by force dissection using an increased imaging force. The thickness of the lower membrane was 6 nm, giving a separation or gap between the two membranes of 2 nm. High-resolution images show fine details of the force-dissected extracellular surfaces, as previously reported for vertebrate and heart gap junctions. In addition high-resolution AFM images show for the first time detailed substructure on the cytoplasmic face of hydrated gap junctions of either vertebrate or invertebrate. The plaques had particles on their exposed and force-dissected faces. These particles were packed in a hexagonal lattice (a = b = 8.9 nm on both faces) and had a diameter of approximately 6.5 nm, with a central, pore-like depression. Fourier maps calculated from the AFM data suggested that each particle was composed of six subunits. These images show a marked similarity to the widely accepted structure of the connexon channel of vertebrate gap junctions.
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PMID:Atomic force microscopy of arthropod gap junctions. 935 88

The fibroblast growth factor (FGF) receptor complex is a ubiquitous regulator of development and adult tissue homeostasis that bridges the peri-cellular matrix and the intracellular environment. Diverse members of the FGF polypeptide family, the FGF receptor tyrosine kinase (FGFRTK) family and the FGF receptor heparan sulfate proteoglycan (FGFRHS) family combine to result in active and specific FGFR signal transduction complexes. Regulated alternate splicing and combination of variant subdomains give rise to diversity of FGFRTK monomers. Divalent cations cooperate with the FGFRHS to conformationally restrict FGFRTK trans-phosphorylation, which causes depression of kinase activity and facilitates appropriate activation of the FGFR complex by FGF. Diffusional and conformational molecular models of the oligomeric FGFR complex are presented to explain how different point mutations in the FGFRTK commonly cause craniofacial and skeletal abnormalities of graded severity by graded increases in FGF-independent activity of total FGFR complexes. The role of the FGF family in liver growth and function and in prostate tumor progression is discussed.
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PMID:The heparan sulfate-fibroblast growth factor family: diversity of structure and function. 942 42

The body's general response to serious thermal injury is characterized by increased vascular permeability immediately after injury and subsequent hypovolemic shock. Skeleto-muscular proteolysis, lipolysis, gluconeogenesis, increased metabolic rate, and a severe systemic inflammatory response induced by local infections or surgical procedures. The increased vascular permeability is mediated by histamine and numerous vasoactive substances, including serotonin, bradykinin, prostaglandins, leukotrienes, and platelet activating factor. Hyper-metabolism is mediated by hormones such as catecholamines, glucagon, and particularly cortisol. In addition, among the putative mediators of the metabolic response to injury, attention has recently been focused on cytokines and lipid mediators which are mainly produced by activated reticuloendothelial cells. Cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor and cortisol responses are interrelated, since cytokines activate the hypothalamo-adrenal axis. The cytokine storm seen in burn patients may be associated with depression of the immune system and with susceptibility to infection. Thermal injury can also lead to activation of the renin-angiotensin-aldosterone system, increased ADH production, and production of atrial natriuretic polypeptide to maintain the circulatory volume. Burn wound infections or surgical procedures can produce and perpetuate a mediator-induced systemic inflammatory response that may lead to multiple organ failure. Serum levels of interleukin-6 are very sensitive to surgical stress, and may be a useful indicator of the general condition of severely burned patients.
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PMID:[Pathophysiologic changes in patients with severe burns: role of hormones and chemical mediators]. 954 40

Administration of hormones to humans and animals results in specific effects on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies with pulsatile administration of various neuropeptides in young and old normal controls and in patients with depression suggest they play a key role in sleep-endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute to sleep-endocrine aberrations during normal ageing and acute depression. In addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly, somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH, probably by feedback inhibition of CRH. Neuroactive steroids exert specific effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A) receptor modulation.
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PMID:Effects of hormones on sleep. 955 Jan 12

A recombinant Fv construct of the B1 monoclonal antibody that recognizes the LewisY-related carbohydrate epitope on human carcinoma cells has been prepared. The Fv is composed of the polypeptide chains of the VH and VL domains expressed independently and isolated as inclusion bodies. The Fv is prepared by combining and refolding equimolar amounts of guanidine chloride solubilized inclusion bodies. The Fv is stabilized by an engineered interchain disulfide bridge between residues VL100 and VH44. This construct has a similar binding affinity as that of the single-chain construct (Benhar and Pastan, Clin. Cancer Res. 1:1023-1029, 1995). The B1 disulfide-stabilized Fv (BldsFv) crystallizes in space group P6(1)22 with the unit cell parameters a = b = 80.1 A, and c = 138.1 A. The crystal structure of the BldsFv has been determined at 2.1-A resolution using the molecular replacement technique. The final structure has a crystallographic R-value of 0.187 with a root mean square deviation in bond distance of 0.014 A and in bond angle of 2.74 degrees. Comparisons of the BldsFv structure with known structures of Fv regions of other immunoglobulin fragments shows closely related secondary and tertiary structures. The antigen combining site of BldsFv is a deep depression 10-A wide and 17-A long with the walls of the depression composed of residues, many of which are tyrosines, from complementarity determining regions L1, L3, H1, H2, and H3. Model building studies indicate that the LewisY tetrasaccharide, Fuc-Gal-Nag-Fuc, can be accommodated in the antigen combining site in a manner consistent with the epitope predicted in earlier biochemical studies (Pastan, Lovelace, Gallo, Rutherford, Magnani, and Willingham, Cancer Res. 51:3781-3787, 1991). Thus, the engineered disulfide bridge appears to cause little, if any, distortion in the Fv structure, making it an effective substitute for the B1 Fab.
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PMID:Crystal structure of the disulfide-stabilized Fv fragment of anticancer antibody B1: conformational influence of an engineered disulfide bond. 959 87

A new type of antifreeze protein was isolated from the serum of the longhorn sculpin, Myoxocephalus octodecimspinosis, by gel filtration and high-performance liquid chromatography. This protein (LS-12) exhibits freezing point depression activity (thermal hysteresis) and ice crystal modification properties similar to those seen for other types of fish antifreeze polypeptide, except that ice crystals grow as hexagonal trapezohedra in the presence of LS-12, rather than hexagonal bipyramids usually seen. Ice crystal etching studies demonstrate that LS-12 does not bind to the hexagonal bipyramidal or secondary prism surfaces reported for the antifreeze polypeptides from winter flounder and shorthorn sculpin, respectively. Circular dichroism studies indicate that LS-12 has an alpha-helix content of about 60% at 1 degreesC, which is in good agreement with a value of about 70% predicted from the amino acid sequence. Limited proteolysis studies and further analysis of the amino acid sequence suggest that LS-12 consists of four amphipathic alpha-helices of similar length which are folded into a four-helix bundle. Based on its size (Mr=12299) and predicted tertiary structure, LS-12 can be regarded as the first example of a new class (type IV) of fish antifreeze protein.
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PMID:Isolation and characterization of an antifreeze protein from the longhorn sculpin, Myoxocephalus octodecimspinosis. 985 55

Antifreeze polypeptides from fish are generally thought to inhibit ice crystal growth by specific adsorption onto ice surfaces and preventing addition of water molecules to the ice lattice. Recent studies have suggested that this adsorption results from hydrogen bonding through the side chains of polar amino acids as well as hydrophobic interactions between the non-polar domains on the ice-binding side of antifreeze polypeptides and the clathrate-like surfaces of ice. In order to better understand the activity of one of the antifreeze polypeptide families, namely the alpha-helical type I antifreeze polypeptides, four alpha-helical peptides having sequences not directly analogous to those of known antifreeze polypeptides and containing only positively charged and non-polar side chains were synthesized. Two peptides with regularly spaced lysine residues, GAAKAAKAAAAAAAKAAKAAAAAAAKAAKAAGGY-NH2 and GAALKAAKAAAAAALKAAKAAAAAALKAAKAAGGY-NH2, showed antifreeze activity, albeit weaker than seen in natural antifreeze polypeptides, by the criteria of freezing point depression (thermal hysteresis) and ice crystal modification to a hexagonal trapezohedron. Peptides with irregular spacing of Lys residues were completely inactive. Up to now, lysine residues have not been generally associated with antifreeze activity, though they have been implicated in some antifreeze polypeptides. This work also shows that lysine residues in themselves, when properly positioned on an alpha-helical polyalanine scaffold, have all the requisite properties needed for such an activity.
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PMID:Artificial antifreeze polypeptides: alpha-helical peptides with KAAK motifs have antifreeze and ice crystal morphology modifying properties. 1043 7

Human melanoma, G361, which induces cachexia in nude mice, has been shown to produce a proteolysis-inducing factor (PIF) of Mr 24000, which is immunologically identical to that isolated from a cachexia-inducing murine tumour (MAC16). Biosynthetic labelling of G361 cells using a combination of [35S]sulphate and [6-3H]glucosamine gave a single component of Mr 24000 after affinity chromatography employing a murine monoclonal antibody. The material contained both radiolabels and, after digestion with peptide N-glycosidase F, two fragments were produced of Mr 14000 and 10000 also containing both radiolabels. Digestion with O-glycosidase produced three fragments of Mr 14000, 6000 and 4000, the first two of which contained both radiolabels, while the third only contained 3H. This digestion pattern is the same as that previously observed with PIF from the MAC16 tumour and is commensurate with one N-linked sulphated oligosaccharide chain of Mr 10000, one O-linked sulphated oligosaccharide chain of Mr 6000 and a central polypeptide chain of Mr 4000 with some residual carbohydrate. When PIF from G361 cells was administered to female NMRI mice (20 g) a pronounced depression of body weight (1.36+/-0.36 g; P < 0.0001 from control) was observed over a 24 h period without a decrease in either food or water consumption. Body composition analysis showed a significant decrease in the non-fat carcass mass without a change in carcass fat or body water. This result suggests that depletion of lean body mass in mice bearing G361 melanoma arises from the production of PIF.
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PMID:Role of a proteolysis-inducing factor (PIF) in cachexia induced by a human melanoma (G361). 1046 89

A detailed understanding of GABAB receptor assembly is an important issue in view of its role as attractive target for treatment of epilepsy, anxiety, depression, cognitive defects, and nociceptive disorders. Heteromerization of GABAB-R1 and GABAB-R2 subunits is a prerequisite for the formation of a functional GABAB receptor. Each individual subunit contains one stretch of approximately 30 amino acid residues within its intracellular C-terminal domain that mediates heteromer formation. To investigate the mechanism of the GABAB-R1/GABAB-R2 interaction and to assess the subunit stoichiometry of the complex, recombinant polypeptide chain fragments containing the heteromerization site were produced by heterologous gene expression in Escherichia coli. When mixed in equimolar amounts, these peptides preferentially formed parallel coiled-coil heterodimers under physiological buffer conditions. This demonstrates that the short C-terminal regions are sufficient to determine the specificity of interaction between GABAB receptor subunits. In contrast, isolated GABAB-R1 peptides folded into relatively unstable homodimers, whereas GABAB-R2 peptides were largely unstructured. Together with the data reported in the literature, the results presented here indicate that the functional GABAB receptor is a heterodimer assembled by parallel coiled-coil alpha-helices.
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PMID:Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices. 1052 99


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