Receptor density balances signal stimulation and attenuation in membrane-assembled complexes of bacterial chemotaxis signaling proteins

All cells possess transmembrane signaling systems that function in the environment of the lipid bilayer. In the Escherichia coli chemotaxis pathway, the binding of attractants to a two-dimensional array of receptors and signaling proteins simultaneously inhibits an associated kinase and stimulates receptor methylation—a slower process that restores kinase activity. These two opposing effects lead to robust adaptation toward stimuli through a physical mechanism that is not understood. Here, we provide evidence of a counterbalancing influence exerted by receptor density on kinase stimulation and receptor methylation. Receptor signaling complexes were reconstituted over a range of defined surface concentrations by using a template-directed assembly method, and the kinase and receptor methylation activities were measured. Kinase activity and methylation rates were both found to vary significantly with surface concentration—yet in opposite ways: samples prepared at high surface densities stimulated kinase activity more effectively than low-density samples, whereas lower surface densities produced greater methylation rates than higher densities. FRET experiments demonstrated that the cooperative change in kinase activity coincided with a change in the arrangement of the membrane-associated receptor domains. The counterbalancing influence of density on receptor methylation and kinase stimulation leads naturally to a model for signal regulation that is compatible with the known logic of the E. coli pathway. Density-dependent mechanisms are likely to be general and may operate when two or more membrane-related processes are influenced differently by the two-dimensional concentration of pathway elements.     

Development of echocardiographic and Doppler parameters after orthotopic cardiac transplantation, except during rejection periods

The aim of this study was to evaluate spontaneous changes of Doppler and echocardiographic parameters of cardiac transplants in the absence of rejection. Based on 258 recordings representing the follow up of 30 patients after orthotopic cardiac transplantation in the absence of histological signs of rejection on biopsy within 24 hours, we tried to define: the evolution of these parameters from the first postoperative week to after the 30th month (average 12 months); the Doppler echocardiographic values of "normal" transplants: the values observed one year after surgery were compared with a control group age-matched to the donors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of total parenteral nutrition on gastric acid secretion

While total parenteral nutrition is widely used, its effects on gastrointestinal function are not well understood. We measured acid secretion in 11 patients during total parenteral nutrition. Five of these patients were retested at least one month after resuming oral intake. Total parenteral nutrition significantly stimulated acid secretion compared to saline infusion (5.5±2.0 vs 1.8±0.6 mEq H⁺/hr,P<0.001) (mean±sem), especially in those patients who are hypersecretors. There was no difference in pentagastrin-stimulated maximal acid output during TPN or saline infusion. Basal and pentagastrin-stimulated acid secretion were similar during and after a course of total parenteral nutrition, suggesting that gastric atrophy did not occur during total parenteral nutrition therapy.Supported by grants from the National Foudation for Ileitis and Colitis, Veterans Administration Career Development Program [Dr. Levine, (RA 1009)] and McGaw Laboratories.Presented, in part, at the 80th Annual Meeting at The American Gastroenterological Association, New Orleans, Louisiana, May 23, 1979.     

Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome

OBJECTIVE: Obese women with polycystic ovary syndrome have a greater frequency of menstrual disturbance and of hirsutism than lean women with the syndrome. Initial studies have demonstrated a marked improvement in endocrine function following a short-term, very low calorie diet. The purpose of this study was to examine the effect of long-term calorie restriction on clinical as well as biochemical abnormalities in obese women with polycystic ovary syndrome. DESIGN: We performed a within-group comparison of clinical and biochemical indices before and during dietary treatment. PATIENTS: Twenty-four obese women with polycystic ovary syndrome (mean weight 91.5 (SD 14.7) kg) were scheduled for treatment for 6-7 months with a 1000 kcal, low fat diet. Nineteen of the 24 had menstrual disturbances, 12 had infertility and 19 were hirsute. MEASUREMENTS AND RESULTS: Thirteen subjects lost more than 5% of their starting weight (range 5.9-22%). In this group there was no significant change in gonadotrophin or total serum testosterone levels but there was a marked increase in concentrations of sex hormone-binding globulin (pretreatment: 23.6 (9.5); post-treatment 36.3 (11.8) nmol/l, P = 0.002) and a reciprocal change in free testosterone levels (77 (26) vs 53 (21) pmol/l, P = 0.009). These changes were accompanied by a reduction in fasting serum insulin levels (median (range) 11.2 (5.2-32) vs 2.3 (0.1-13.8) mU/l, P = 0.018) and the insulin response to 75 g oral glucose. There were no significant changes in these indices in the group who lost less than 5% of their initial body weight. Of the 13 women who lost greater than 5% of their pretreatment weight, 11 had menstrual dysfunction. Amongst these women, nine of 11 showed an improvement in reproductive function, i.e. they either conceived (five) or experienced a more regular menstrual pattern. There was a reduction in hirsutism in 40% of the women in this group. By contrast, in the group who lost less than 5% of their initial weight, only one of the eight with menstrual disturbances noted an improvement in reproductive function and none had a significant reduction in hirsutism. CONCLUSIONS: These data indicate that moderate weight loss during long-term calorie restriction is associated with a marked clinical improvement which reflects the reduction in insulin concentrations and reciprocal changes in SHBG. The improvement in menstrual function and fertility may therefore be consequent upon an increase in insulin sensitivity which, directly or indirectly, affects ovarian function.     

Illness severity, viral shedding, and antibody responses in infants hospitalized with bronchiolitis caused by respiratory syncytial virus

The relationships between host factors, viral shedding, illness severity, and antibody response in respiratory syncytial virus (RSV)-induced bronchiolitis are poorly defined. These relationships were prospectively evaluated in 77 infants hospitalized with RSV bronchiolitis in multicenter, double-blind, placebo-controlled trials of RSV immunoglobulin therapy. Severity of illness was influenced by age and host risk factors but was not influenced by RSV neutralizing antibody titer or by the amount of virus in nasal secretions at enrollment. Virus recovery in nasal secretions was variable but was highest at enrollment. Viral shedding was not influenced by primary diagnosis, antibody titer, age, or duration of acute respiratory illness before enrollment. In intubated patients, the amounts of virus recovered in nasal secretions and endotracheal aspirates were highly correlated. A serum neutralizing antibody response was seen in 64% of subjects who received placebo. The response was not influenced by age, primary diagnosis, amount of virus recovered, or severity of illness but was suppressed by preexisting antibody.     

Strict versus lenient weight criterion in anorexia nervosa

The present study evaluates the current BMI cut‐off for diagnosing anorexia nervosa. Physical state, eating disorder and general psychopathology were compared in two groups diagnosed with anorexia nervosa, using ‘strict’ or ‘lenient’ weight criteria (above or below the generally accepted BMI cut‐off of 17.5 kg/m²). Individuals in the lenient group had a higher percentage body fat and a greater discrepancy between current and ideal body weight, but there were no differences between the two groups on other body image measures. The strict group had met criteria for strict anorexia nervosa for a greater proportion of the past 5 years, but there was no difference in the number of months with anorexia nervosa. On all other variables, the two groups were indistinguishable. These results challenge the cut‐off of BMI 17.5 kg/m² in the diagnosis of anorexia nervosa. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.     

Skin thickness changes in normal aging skin

The age-dependent decrease of skin thickness was studied with a morphometric procedure on upper inner arm skin biopsies. Epidermal thickness decreased somewhat faster in men (7.2% of the original value/decade) than in women (5.7%). The total dermal thickness decreased at about the same rate in men and women (6%/decade). The thickness of the superficial layer of the dermis exhibited a biphasic evolution with age and these variations were not significantly different between men and women because of the large individual variations. This may be due partially to the difficulties of delineating with precision the limit between superficial and reticular dermis. These results are somewhat lower than those obtained by physical measurements of skin thickness. This may be due to fixation artifacts and also to the overestimation of skin thickness by physical measurements.     

Within-group differences in depression among older Hispanics living in the United States

Using the Health and Retirement Study, we examine the prevalence of depression in different groups of Hispanic older adults. Respondents (n = 759) were aged 59 and older and identified themselves as Mexican American (56%), Cuban American (13%), Puerto Rican (8%), other (8%), or not specified (15%). We used a modified version of the Center for Epidemiologic Studies-Depression scale and the Composite International Diagnostic Interview to assess depressive symptoms and the presence of major depression. Relative to Puerto Ricans, each Hispanic group had significantly lower levels of depressive symptoms, except for Cuban Americans; and each Hispanic group had lower prevalence rates for major depression, except for other Hispanics, even after we adjusted for sociodemographic, cultural factors, socioeconomic, functional limitations, and chronic health conditions.