Citations

The pathogenic fungus Pneumocystis carinii causes severe pneumonia in patients with impaired immunity, particularly patients with acquired immunodeficiency syndrome. The life cycle of P. carinii is poorly understood, and the inability to continuously culture P. carinii is a major limitation in understanding its cell biology. In fungi homologous to P. carinii, pheromone mating factors signal through a mitogen-activated protein kinase (MAPK) signal transduction cascade, resulting in mitotic cell cycle arrest and entry into a pathway of conjugation, cellular differentiation, and proliferation. Using degenerate PCR and library screening, we have identified a MAPK cDNA in P. carinii that is highly homologous to fungal MAPKs involved in the pheromone mating signal transduction cascade, and we demonstrate MAPK activity in P. carinii lysates with a specific antiserum derived from the translated P. carinii MAPK cDNA sequence.

Nonexercise activity thermogenesis (NEAT) accounts for the vast majority of nonresting metabolic rate and changes in NEAT-predicted susceptibility to fat gain with overfeeding. Measuring physical activity and its components in free-living humans has been a long-standing challenge. In this study, we combine information about lightweight sensors that capture data on body position and motion with laboratory measures of energy expenditure to calculate nonfidgeting NEAT. This measurement of nonfidgeting NEAT was compared with total NEAT measured in a room calorimeter in 11 healthy subjects. The measurement of nonfidgeting NEAT accounted for 85 ± 9% of total NEAT measured in the room calorimeter. The intraclass correlation coefficient for the two methods was 0.86 (95% confidence interval 0.56, 0.96; P < 0.05). This suggests that 86% of the variance is attributable to between-subject variance and 14% to between-method disagreement. These instruments are applicable to free-living subjects; they are stand-alone, are lightweight, and allow normal daily activities. This novel technology has potential application for not only assessing NEAT but also tracking physical activity in free-living humans.

To investigate the underlying molecular mechanisms for surgery-induced insulin resistance in skeletal muscle, six otherwise healthy patients undergoing total hip replacement were studied before, during, and after surgery. Patients were studied under basal conditions and during physiological hyperinsulinemia (60 μU/ml). Biopsies of vastus lateralis muscle were used to measure GLUT-4 translocation, glucose transport, and glycogen synthase activities. Surgery reduced insulin-stimulated glucose disposal ( P < 0.05) without altering the insulin-stimulated increase in glucose oxidation or suppression of endogenous glucose production. Preoperatively, insulin infusion increased plasma membrane GLUT-4 in all six subjects ( P < 0.05), whereas insulin-stimulated GLUT-4 translocation only occurred in three patients postoperatively (not significant). Moreover, nonoxidative glucose disposal rates and basal levels of glycogen synthase activities in muscle were reduced postoperatively ( P< 0.05). These findings demonstrate that peripheral insulin resistance develops immediately postoperatively and that this condition might be associated with perturbations in insulin-stimulated GLUT-4 translocation as well as nonoxidative glucose disposal, presumably at the level of glycogen synthesis.

Growth hormone excess can cause postprandial carbohydrate intolerance. To determine the contribution of splanchnic and extrasplanchnic tissues to this process, subjects were fed an isotopically labeled mixed meal after either a 12-h infusion of saline or growth hormone (4 micrograms.kg-1.h-1 [corrected]). Growth hormone infusion resulted in higher glucose and insulin concentrations both before and after meal ingestion. Despite growth hormone-induced hyperglycemia and hyperinsulinemia, postprandial hepatic glucose release and carbon dioxide incorporation into glucose (a qualitative estimate of gluconeogenesis) were similar to those present during saline, suggesting altered hepatic regulation. This was confirmed when glucose was infused in the absence of growth hormone to achieve glucose (and insulin) concentrations comparable to those present during growth hormone infusion. Although growth hormone excess did not alter splanchnic uptake of ingested glucose, it resulted in a fivefold increase in postprandial hepatic glucose release (578 +/- 31 vs. 117 +/- 10 mg.kg-16 h-1, P less than 0.01), less suppression of carbon dioxide incorporation into glucose (-13 +/- 9 vs. -53 +/- 12 mg.kg-1. 6-h-1, P less than 0.01), and lower glucose uptake (1,130 +/- 59 vs. 1,850 +/- 150 mg.kg-1.6 h-1, P less than 0.01). The decrease in postprandial glucose uptake did not appear to be mediated by a change in substrate uptake since postprandial plasma concentrations and forearm balance of lactate, free fatty acids, and ketone bodies did not differ in the presence and absence of growth hormone excess.(ABSTRACT TRUNCATED AT 250 WORDS)

Recordings of pressure and electric potentials from Biebl loops of the duodenum of trained dogs were used to quantitate and to determine relationships among basic electric rhythm (BER), irregular bursts of spike potentials, and motor action of the duodenum. After control periods, morphine was used to stimulate rhythmic motor activity. The omnipresence of a stable, longitudinally propagated BER was demonstrated, each phase of which was detected simultaneously by electrodes arranged radially in the wall of the gut. Spike potentials were recorded whenever contraction of the gut wall was detected. The spikes occurred during a limited segment of the BER. Their number and amplitude were directly related to the strength of the contractions. Under control conditions, duodenal contractions associated with the spike potentials produced type I waves in the pressure record. Neither the spike potentials nor the type I contractions were conducted more than a few centimeters. With morphine only the latter portion of the BER showed minor changes. Incidence of spike potentials and contractions was increased. Occasionally morphine induced motor spasms, accompanied by a prolonged series of spike-like potentials and disruption of the BER.

In preparation for a study of the electric activity in the wall of the gastroduodenal junction in unanesthetized trained dogs, the pyloric portion of the stomach (antrum), the pylorus, and the first portion of the duodenum were exteriorized surgically. When the animals were fully recovered, needle electrodes were inserted into the wall of the bowel for the detection of electric activity. The pylorus was found to act as an "electric insulator" between the stomach and the duodenum. The basic electric rhythm (BER) and the fast or spike activity detected in both the pyloric canal and the duodenal bulb became attenuated in the pylorus and usually disappeared in it. The BER of the antrum had a mean frequency of 4.4 cycle/min and spike potentials sometimes were associated with it. The frequency of the BER in the duodenal bulb was the same as in the duodenum but its voltage was less and its form more irregular. Spike potentials in the bulb occurred during a greater portion of the BER and had a greater tendency to distort the BER than in the more distal duodenum.

After a preliminary observation period, a small lesion was made in the pituitary stalk of 10 dogs. The daily water intake, urinary output, urinary specific gravity and body weight were recorded. Each animal was given water-load tests consisting of a large volume of tap water by gavage. The surgical lesions were verified histologically. Immediately following the surgical procedure there was a marked spontaneous increase in water intake and urinary output lasting approximately 3 days. Each animal subsequently passed through a period of water retention as shown by the water-load test at some time between the 6th and the 10th postoperative day. Following this, the water exchange and the response to the water-load test approximated the preoperative values. The possible physiologic significance of these findings is discussed.

Action potentials of single vagal afferent nerve fibers from slowly adapting pulmonary stretch receptors, transpulmonary pressure and rate of air flow were recorded in anesthetized cats with open thoraxes during varied volumes and rates of inflation and deflation of the lungs. Both discharge frequency and total transpulmonary pressure varied with lung volume and also with its rate and sign of change. Effects of acceleration of volume on discharge frequency were not observed. The receptors provide signals related to the work of breathing.