Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women

BACKGROUND: On the basis of observations in rodents, leptin is thought to play a key role in the regulation of energy expenditure and food intake, but less is known of its influence on ingestive behavior and energy balance in humans. OBJECTIVE: We examined the effect in women of a chronic energy deficit on plasma leptin concentrations and self-reported appetite and explored possible relations between leptin and appetite sensations. DESIGN: Twelve healthy women (body mass index, in kg/m2: 23-37) participated in a metabolic ward study in which 3 wk of neutral energy balance was followed by 12 wk of energy deficit (energy intake reduced by 2 MJ/d and energy expenditure increased by 0.8 MJ/d). Body weight and composition were monitored, fasting leptin concentrations were measured 4 times, and feelings of hunger, fullness, desire to eat, and prospective consumption were monitored hourly throughout the day on 7 selected days. RESULTS: Adiposity-adjusted leptin decreased by 54% after 1 wk of a moderate energy deficit and remained low after 6 and 12 wk. Leptin was associated with self-reported hunger, desire to eat, and prospective consumption (range of r: -0.6 to -0.7, P < 0.01). The greatest hunger increase coincided with the largest percentage drop in circulating leptin and the lowest final leptin concentration. The relation between leptin and hunger was not influenced by amount of weight or body fat loss. CONCLUSIONS: These findings support the idea that leptin is a physiologic regulator of hunger during energy deficits in humans; the role of leptin in the long-term regulation of food intake warrants further study.     

Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey

Prefrontal cortices have been implicated in autonomic function, but their role in this activity is not well understood. Orbital and medial prefrontal cortices receive input from cortical and subcortical structures associated with emotions. Thus, the prefrontal cortex may be an essential link for autonomic responses driven by emotions. Classic studies have demonstrated the existence of projections between prefrontal cortex and the hypothalamus, a central autonomic structure, but the topographic organization of these connections in the monkey has not been clearly established. We investigated the organization of bidirectional connections between these areas in the rhesus monkey by using tracer injections in orbital, medial, and lateral prefrontal areas. All prefrontal areas investigated received projections from the hypothalamus, originating mainly in the posterior hypothalamus. Differences in the topography of hypothalamic projection neurons were related to both the location and type of the target cortical area. Injections in lateral eulaminate prefrontal areas primarily labeled neurons in the posterior hypothalamus that were equally distributed in the lateral and medial hypothalamus. In contrast, injections in orbitofrontal and medial limbic cortices labeled neurons in the anterior and tuberal regions of the hypothalamus and in the posterior region. Projection neurons targeting orbital limbic cortices were more prevalent in the lateral part of the hypothalamus, whereas those targeting medial limbic cortices were more prevalent in the medial hypothalamus. In comparison to the ascending projections, descending projections from prefrontal cortex to the hypothalamus were highly specific, originating mostly from orbital and medial prefrontal cortices. The ascending and descending connections overlapped in the hypothalamus in areas that have autonomic functions. These results suggest that specific orbitofrontal and medial prefrontal areas exert a direct influence on the hypothalamus and may be important for the autonomic responses evoked by complex emotional situations.     

Optical amplification of ligand-receptor binding using liquid crystals

Liquid crystals (LCs) were used to amplify and transduce receptor-mediated binding of proteins at surfaces into optical outputs. Spontaneously organized surfaces were designed so that protein molecules, upon binding to ligands hosted on these surfaces, triggered changes in the orientations of 1- to 20-micrometer-thick films of supported LCs, thus corresponding to a reorientation of approximately 10(5) to 10(6) mesogens per protein. Binding-induced changes in the intensity of light transmitted through the LC were easily seen with the naked eye and could be further amplified by using surfaces designed so that protein-ligand recognition causes twisted nematic LCs to untwist. This approach to the detection of ligand-receptor binding does not require labeling of the analyte, does not require the use of electroanalytical apparatus, provides a spatial resolution of micrometers, and is sufficiently simple that it may find use in biochemical assays and imaging of spatially resolved chemical libraries.     

Clinical relevance of parvovirus B19 as a cause of anemia in patients with human immunodeficiency virus infection

Parvovirus B19 (B19) DNA was detected by dot blot hybridization in sera from 5 (17%) of 30 human immunodeficiency virus (HIV)-infected patients with hematocrits (HCT) of < or =24 and 4 (31%) of 13 HRV-infected patients with HCT of < or =20, suggesting that B19 is a reasonably common cause of severe anemia in HIV infection. The anemia promptly remitted after immunoglobulin therapy in 3 of 4 treated patients. The presence of IgM to B19, the clinical circumstance in which anemia developed, and the marrow morphology were poor predictors of chronic B19 infection. DNA hybridization studies of sera from 191 HIV-infected and 117 HIV-seronegative homosexual males attending a clinic in the Seattle area revealed that 1 (0.5%) and 2 (2%) samples, respectively, from the 2 groups contained B19. However, when assayed by polymerase chain reaction (PCR), 5% of the serum samples from HIV-infected persons and 9% from uninfected persons contained B19, although each had an HCT of > or =40. The data argue that anemia results from chronic high-titer B19 infection. Although a negative PCR assay excludes this diagnosis, DNA hybridization may be the more specific serum test.     

Characterization of mat A-2, mat A-3 and deltamatA mating-type mutants of Neurospora crassa

The mating-type locus of Neurospora crassa regulates mating identity and entry into the sexual cycle. The mat A idiomorph encodes three genes, mat A-1, mat A-2, and mat A-3. Mutations in mat A-1 result in strains that have lost mating identity and vegetative incompatibility with mat a strains. A strain containing mutations in both mat A-2 and mat A-3 is able to mate, but forms few ascospores. In this study, we describe the isolation and characterization of a mutant deleted for mat (deltamatA), as well as mutants in either mat A-2 or mat A-3. The deltamatA strain is morphologically wild type during vegetative growth, but it is sterile and heterokaryon compatible with both mat A and mat a strains. The mat A-2 and mat A-3 mutants are also normal during vegetative growth, mate as a mat A strain, and produce abundant biparental asci in crosses with mat a, and are thus indistinguishable from a wild-type mat A strain. These data and the fact that the mat A-2 mat A-3 double mutant makes few asci with ascospores indicate that MAT A-2 and MAT A-3 are redundant and may function in the same pathway. Analysis of the expression of two genes (sdv-1 and sdv-4) in the various mat mutants suggests that the mat A polypeptides function in concert to regulate the expression of some sexual development genes.     

Technical report: Cystic air spaces in the lung: change in size on expiratory high-resolution CT in 23 patients

BACKGROUND: Urticaria is a common disease that is always a challenge to the dermatologist due to its evasive etiology. PATIENTS AND METHODS: One hundred and seven chronic urticaria patients were studied. Routine laboratory investigations were performed and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody determinations, autoimmune reactivity, infections, allergies, and hyperreactivities were investigated. RESULTS: Pathologic findings were seen in 92 patients. Concomitant diseases suggesting autoimmune reactivity were detected in nine patients and, in 16 patients, infections including maxillary sinusitis, streptococcal tonsillitis, and tooth infection were found. Elevated total IgE level was detected in 37 out of 75 patients and positive skin prick test results in 47 out of 91 patients. Fifty-five patients had a history of recent dyspeptic symptoms. A diagnosis of adult celiac disease was made in two patients and, additionally, IgA antigliadin antibodies were seen in four patients. H. pylori IgG antibodies were found in 40 out of 107 patients. Active gastritis was verified by esophagogastroduodenoscopy in 30 out of 32 patients with positive Helicobacter staining in 24 samples. An elevated IgE level was detected in 64% of H. pylori-positive and in 39% of H. pylori-negative patients. CONCLUSIONS: In this study, several findings suggesting aberrant immunologic activation were detected in chronic urticaria patients. Inflammation in the gastrointestinal tract, e.g. caused by H. pylori infection, may have an important role in the etiology of chronic urticaria.     

EEG pharmacodynamics upon single administration of seduxen in healthy volunteers

We have examined the type I collagen protein, RNA, and cDNA of 2 children with moderately severe (type IV) osteogenesis imperfecta (OI). They have in common a non-lethal form of OI with ambulatory potential, overmodification of type I collagen protein, and a substitution of serine for glycine in the collagen chain produced by one alpha 1(I) allele. The first child (Marini et al.: J Biol Chem 264:11893-11900, 1989) is now 7 years old, with the height of a 3-year-old. Her course includes significant remodeling of lower long bones and 4 femur fractures. She walks independently. A mishmatch was detected in her alpha 1(I) mRNA using RNA/RNA hybrids; it was demonstrated to be due to a G-->A point mutation in one allele of alpha 1(I), resulting in the substitution of serine for glycine 832. The second child is now 6 1/2 years old, with the height of 1 1/2-year-old. Her history includes significant bowing of femurs and tibias, 6 femur fractures, S-curve scoliosis, compression of all lumbar vertebrae, and limited short-distance walking with braces. Her alpha 1(I) mRNA has also been studied by RNA hybrid analysis; there is a single G-->A change in one alpha 1(I) allele causing the substitution of serine for gly 352. Both children have moderately severe OI. However, the serine substitution at gly 352 is associated with a more severe phenotype then is the serine substitution at gly 832. Compared to substitutions described in other cases of OI, the serine 352 is located in the middle of a cluster of cysteine substitutions associated with non-lethal OI.(ABSTRACT TRUNCATED AT 250 WORDS)