The distribution of fat in the body differs between the male and female sexes and is associated with the relative secretion of the two "adiposity" hormones leptin and insulin. We now report that the brains of male and female rats are differentially sensitive to the catabolic actions of small doses of these two hormones. Leptin (1 or 3.5 g/2 l) or saline (2 l) was administered into the third cerebral ventricle of age-and weight-matched male and female rats. Leptin significantly reduced food intake in female and male rats over 4 h; however, leptin reduced 24-h intake in female but not in male rats. When the same rats were administered insulin (1 or 4 mU/2 l) or saline (2 l), male but not female rats had a robust reduction in food intake over 24 h. Previous research demonstrates the melanocortins are a central mediator of the effects of both leptin and insulin. However, we found no sex differences in sensitivity to the melanocortin agonist MTII (0.01, 0.1, 0.3, and 1.0 nmol/2 l). These results suggest that the sex differences in sensitivity to leptin and insulin at the doses that we injected occur upstream of the melanocortin receptors. Because insulin and leptin reflect different fat beds and are differentially distributed in the male and female sexes, the implication is that the male and female sexes regulate adiposity-relevant parameters differently. Diabetes 52:682-687, 2003 T he increasing prevalence of obesity throughout the world is associated with an escalating incidence of obesity-related disorders and health costs (1,2). One of the more important discoveries in recent years was the finding that the distribution of fat within the body is associated with the risk for developing obesity-related complications (3). Fat distributed in the abdominal or visceral region carries a much greater risk for cardiovascular problems, type 2 diabetes, certain cancers, and other disorders than does fat distributed subcutaneously (3,4). Of particular importance to public health is that the distribution of fat varies greatly between men and women. On average, women carry more fat subcutaneously, whereas men carry more fat viscerally (3). Hence, there are major sex differences with regard to obesity-associated health risks, men being more likely to develop cardiovascular problems, diabetes, and other obesity-related problems (5). Because of this, it is vitally important to determine whether there are parallel differences in the way men and women detect and respond to signals that control energy balance and metabolism.Hormones secreted in proportion to body fat provide an important regulatory signal to the brain. In particular, leptin and insulin are each secreted into the plasma in direct proportion to body fat, and each peptide is transported into the brain (6,7), where it acts on specific receptors on neurons in the hypothalamus and other brain areas (8,9). Increased activity of either peptide locally in the vicinity of the ventral hypothalamus causes an overall catabolic response (i.e., reduced food intake, increased energy...

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Addition of biologically active phorbol esters to intact quiescent I3T mouse cells stimulates an extremely rapid (detectable within seconds) phosphorylation of a Mr 80,000 cellular protein (termed "80k"). Phorbol 12,13-dibutyrate enhances 80k phosphorylation in a dose-dependent manner; half-maximal effect is obtained at 32 nM. The possibility that this phosphorylation is related to the activation of Ca'+-activated phospholipid-dependent protein kinase is suggested by the fact that phospholipid breakdown induced by exogenous treatment of the cells with phospholipase C from Clostridium perfrngen8 or with platelet-derived growth factor, which is a potent activator of endogenous phospholipase C activity, also causes a rapid enhancement of 80k phosphorylation. Moreover, prolonged pretreatment of the cells with phorbol 12,13-dibutyrate, which leads to a marked decrease in the number of specific phorbol ester binding sites, prevents the phosphorylation of 80k stimulated by phorbol esters, phospholipase C, and platelet-derived growth factor. These findings provide evidence obtained with intact cells that implicate the stimulation of Ca2'-activated phospholipid-dependent protein kinase in the action of phorbol esters and other growth factors.Tumor promoters are compounds that, although not carcinogenic by themselves, increase the incidence of tumors when applied repeatedly to animals that have received a subthreshold dose of a carcinogen (1). Their mechanism of action is of considerable interest, with attention focusing on their biological effects in various types of cultured cells. In confluent and quiescent mouse 3T3 cells, biologically active phorbol esters bind to a single class of high-affinity sites (2, 3) and rapidly stimulate ion fluxes (4), enhance nucleoside and hexose uptake (5, 6), decrease the affinity of the surface receptors for epidermal growth factor (7-9), induce ornithine decarboxylase activity (10), and subsequently stimulate reinitiation of DNA synthesis when added with other mitogens in serum-free medium (2, 3, 10, 11). Although tumor promoters and hormonal peptides such as vasopressin (12) and bombesin (13) share pathways of action (3, 10, 13), the mechanism whereby occupancy of the phorbol ester receptors leads to the elicitation of their biological responses remains unknown and of considerable importance to gain insight into the molecular events leading to tumor promotion.A type of cyclic nucleotide-independent protein kinase has been discovered that is activated by association with membrane phospholipid& in the presence of Ca2+ (14, 15); the activity of the-membrane-associated enzyme is potently stimulated by unsaturated diacylglycerol (16). Recently, several reports indicate that biologically active phorbol esters can substitute. for diacylglycerol in stimulating the partially purified enzyme incubated in the presence of phospholipids (17-20). Similar observations were made with extracts prepared from Swiss 3T3 cells (our unpublished results). Whether or not these observations in vitro...

Psittacosis, also known as parrot fever and ornithosis, is a bacterial infection of humans that can cause severe pneumonia and other serious health problems. It is caused by Chlamydophila psittaci, formerly known as Chlamydia psittaci. From 1988 through 2003, 935 human cases of psittacosis were reported to the CDC and most resulted from exposure to infected pet birds, usually cockatiels, parakeets, parrots, and macaws. In birds, C. psittaci infection is referred to as avian chlamydiosis. Infected birds shed the bacteria through feces and nasal discharges, and humans become infected from exposure to these materials. This compendium provides information about psittacosis and avian chlamydiosis to public health officials, physicians, veterinarians, the pet bird industry, and others concerned with controlling these diseases and protecting public health. The recommendations in this compendium provide standardized procedures for controlling avian chlamydiosis in birds, a vital step to protecting human health. This document will be reviewed and revised as necessary.

DURING lactation in the rat the alimentary canal shows an increase in weight and nitrogen content compared with that of unmated controls (Poo, Lew and Addis, 1939), or pregnant rats (Boyne, Chalmers and Cuthbertson, 1953; Souders and Morgan, 1957). Po0 et al. included with the alimentary canal the entire contents of the abdomen and pelvis except for the liver, kidneys and uterus, whereas Boyne et al. examined the cleaned and empty gut and Souders and Morgan studied only the small intestine. The determinations were made on the loth day of lactation by Po0 et al., on the 16th day by Boyne et al. and immediately after weaning by Souders and Morgan.We felt that the increase in nitrogen content of the alimentary canal during lactation was suilicient to justify a more detailed study, the results of which are presented in this paper. MATERIALS AND METHODSAnimals and diet. Adult virgin or lactating, prirniparous Hooded Lister female rats were used in these experiments. The food was '' Diet 86 ", compounded as cubes by the North-Eastern Agricultural Coop. Soc. Ltd, Aberdeen. It contained: wheat 50 per cent.; barley 25; white fish meal 7; meat and bone meal 6 ; dried brewers' yeast 5 ; dried grass meal 5 ; sodium chloride 1; and cod liver oil or equivalent stabdised vitamins A and D, 1 per cent. Analysis gave: dry matter 85.7 per cent.; protein 20.0; fat 3.8; soluble carbohydrate (by difference) 53.4; fibre 3.3; and ash 5.2 per cent.Food and water were freely available to dam and litter in all experiments. In some experiments the cubes were milled to facilitate the recording of food consumption. All the lactating rats ate an unrecorded amount of wood-wool litter.Usually the litters were reduced to 8 young per rat on the day of birth, but since the results were apparently not influenced by litter size we have included some early data obtained from rats with litter size greater than 8.Weight of ufimentury d. Lactating rats were killed with ether vapour at daily intervals from the first day postpartum up to the early post-weaning period, at which dates their average body weight was 280 g. They were eviscerated and the omentum, mesentery and fat were removed from the viscera. The length of the small intestine was recorded and Peyer's patch= were counted. The small inhtine was then divided into three equal lengths, which for the purposes of this paper were regarded as corresponding approximately to duodenum, jejunum and ileum; the stomach, caecum and colon were treated separately. The parts were cut open, washed in water, blotted and weighed. Twelve virgin female controls of average body weight 260 g. were treated similarly. In the final experiment the young of primiparous rats were killed on the day I. PA-BMX.--VOL 85 (1963) 179 Acta anat., 43,264. This J o u d , 81,251.

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Previous analyses by fluorescence in situ hybridization of structures present 20-30 cell generations after the primary events of mali gene amplification have shown that tens of megabases of DNA separate each copy of the selected gene in chromosomal arrays that contain up to 15 copies. Since these structures are very unstable, it is neceary to study amplified DNA as soon as possible after it has been formed to relate the structures observed to the primary mechanisms that generated them. Previously, new amplifications of the CAD gene were analyzed in colonies of 105 N-(phosphonoacetyl)-L-aspartate-resistant Syrian hamster BHK cells. CAD is on the p arm of chromosome B9 and the amplified genes were usually found in large extensions of B9p, with one copy in its normal position. We now report that dividing drug-resistant cells have been physically separated from static drug-sensitive cells, to allow the amplified structures to be observed only a few cell generations after they have been formed. The most informative results are that about one-third of the newly formed chromosomes carrying amplified CAD genes are dicentric and that about halfof these carry two B9q arms. These observations reveal that recombination between the p telomeric regions of two B9 sister chromatids is an important primary event of amplification in this system. The resulting dicentric chromosomes can then enter bridge-breakage-fusion cycles that provide the means to increase the number of CAD genes per cell in successive generations by an asymmetric distribution at each cell division.Several recent papers in which fluorescence in situ hybridization has been used to look at structures formed early in gene amplification have shed light on this process and have dramatically changed our ideas about the mechanisms involved. Trask and Hamlin (1) studied methotrexate-resistant populations of Chinese hamster cells derived from a single cell by serial selection with increasing concentrations of drug over a period of about 8 weeks. The amplified dihydrofolate reductase genes were chromosomal and spaced tens of megabases apart. They were located on extended structures derived from the same chromosome arm that carries the single gene in unselected cells. Trask and Hamlin (1) concluded that replicative mechanisms were unlikely to be responsible and favored recombinational mechanisms such as sister chromatid exchange.We studied (2) amplifications of the carbamoyl-P synthetase, aspartate transcarbamylase, dihydroorotase (CAD) gene in Syrian hamster cells resistant to N-(phosphonoacetyl)-L-aspartate (PALA) at a somewhat earlier stage, when colonies had reached about 105 cells. We also saw (2) chromosomally amplified genes tens of megabases apart, usually on the same chromosome arm that carried the CAD gene in unselected cells. Furthermore, there were two strong indications that the structures formed in the initial event had changed considerably by the 105-cell stage: individual cells within a single clone had quite different numbers of CAD genes and som...