Sleep deprivation in the rat: XV. Ambient temperature choice in paradoxical sleep-deprived rats.

Previous studies of total sleep deprivation (TSD) and paradoxical sleep deprivation (PSD) in the rat by the disk-over-water method have indicated that both produce changes in thermoregulation. In both kinds of deprivation, there was a progressive, large increase in heat production as indicated by measures of energy expenditure (EE). In TSD there was an initial increase in waking body temperature (Tb) followed by a later decrease; in PSD there was only a progressive decrease.

Increased stimulatory G protein in neoplastic human thyroid tissues.

Prior studies in our laboratory have shown that thyroid neoplasms produce increased amounts of cyclic adenosine monophosphate (cAMP). Thyroid-stimulating hormone receptors act through the stimulatory G protein (Gs) to activate adenylate cyclase, the enzyme responsible for cAMP production. The purpose of this study is to measure the activity and amount of Gs in human normal and neoplastic thyroid tissue to see whether alterations in Gs are responsible for the increased cAMP production seen in thyroid neoplasms.

Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein.

Activating mutations in the gene for the alpha-chain of Gs, the stimulatory regulator of adenylyl cyclase, have been identified in human GH-secreting pituitary tumors. Using the polymerase chain reaction and allele-specific oligonucleotide hybridization, we screened 25 GH-secreting tumors for the presence of the activating mutations. We also reviewed the clinical charts of the patients from whom the tumors were removed.

Two G protein oncogenes in human endocrine tumors.

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes.

Mutational analysis of the structure and function of GTP-binding proteins.

Structural, biochemical and molecular genetic studies of EF-Tu, p21ras and alpha s have begun to reveal the inner workings of the molecular machine used by these and other GTP-binding proteins. Further understanding of this molecular machine will ultimately come from crystal structures of the G protein alpha chains as well as from crystal structures of the GTP-bound forms of p21ras and EF-Tu. Mutational analysis will continue to add meaning to the static pictures provided by these crystal structures.

GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours.

A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein alpha chain, alpha(s). The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone. Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP.

Differential effects of acetylsalicylic acid and acetaminophen on sleep abnormalities in a rat chronic pain model.

We studied the effects of two non-steroidal anti-inflammatory analgesics (NSAIAs), acetylsalicylic acid (ASA) and acetaminophen, on sleep patterns in rats with adjuvant-induced arthritis. We found that in the normal rat both NSAIAs reduced non-rapid eye movement (NREM) sleep. In arthritic rats ASA and acetaminophen had opposite effects on sleep.

Decreased slow-wave and paradoxical sleep in a rat chronic pain model.

Diurnal sleep-wake patterns in the normal and the adjuvant arthritic rat were measured during the first 3 h of both light and dark periods. During the hours of maximal sleep in the normal rat, arthritic rats showed a significant increase in wakefulness (Wake), a shift to non-rapid-eye-movement (NREM) stages with lower amplitudes (LS and HS1), and a large reduction of NREM sleep with the highest-amplitude (HS2) and paradoxical sleep. Arthritic rats also showed marked sleep fragmentation manifested by more episodes of Wake, LS, and HS1 and shorter episodes of HS2 during both the light and the dark periods.

Hydrolysis of GTP by the alpha-chain of Gs and other GTP binding proteins.

The functions of G proteins--like those of bacterial elongation factor (EF) Tu and the 21 kDa ras proteins (p21ras)--depend upon their abilities to bind and hydrolyze GTP and to assume different conformations in GTP- and GDP-bound states. Similarities in function and amino acid sequence indicate that EF-Tu, p21ras, and G protein alpha-chains evolved from a primordial GTP-binding protein. Proteins in all three families appear to share common mechanisms for GTP-dependent conformational change and hydrolysis of bound GTP.

Sleep fragmentation in the arthritic rat.

We examined the diurnal sleep-wake patterns in the adjuvant arthritic rat. In contrast to control rats, arthritic rats lacked a normal diurnal variation in sleep and wakefulness. Thus, arthritic rats exhibited no differences in the mean number or duration of bouts of sleep and episodes of wakefulness between light and dark hours.

Effect of carbachol on radiosodium uptake by dispersed pancreatic acinar cells.

The effects of carbachol on uptake of 22Na by enzymatically dispersed rat pancreatic acinar cells were determined. Carbachol caused a slight but significant increase in uptake of 22Na by the cells in the presence of absence of ouabain (10(-3) M). A maximal response was obtained with 10(-6) M carbachol.

Dose-response relation of CSF sodium and renal sodium excretion, and its absence in homozygous Brattleboro rats.

Constant intraventricular infusion (3.3--6.6 microliters/min) of artificial cerebrospinal fluid with sodium concentrations of 100, 150, 200, 250, 300, and 350 mM produced a linear dose-related change in renal sodium excretion in conscious, unrestrained Sprague-Dawley rats.

Calcium and receptor regulation of radiosodium uptake by dispersed rat parotid acinar cells.

1. Dispersed rat parotid acinar cells were used to study the effects of secretagogues on 22Na uptake. 2.

Relationship between calcium release and potassium release in rat parotid gland.

1. A study was made of the role of Ca release in mediating the sustained phase of K release (86 Rb release) in the rat parotid gland due to receptor activation. 2.