Resting (basal) secretion of proteins is provided by the minor regulated and constitutive-like pathways and not granule exocytosis in parotid acinar cells.

Resting secretion of salivary proteins by the parotid gland is sustained in situ between periods of eating by parasympathetic stimulation and has been assumed to involve low level granule exocytosis. By using parotid lobules from ad libitum fed rats stimulated with low doses of carbachol as an in vitro analog of resting secretion, we deduce from the composition of discharged proteins that secretion does not involve granule exocytosis. Rather, it derives from two other acinar export routes, the constitutive-like (stimulus-independent) pathway and the minor regulated pathway, which responds to low doses of cholinergic or beta-adrenergic agonists (Castle, J.

Experimental annotation of the human genome using microarray technology.

The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons.

Exclusion limits on the WIMP-nucleon cross section from the cryogenic dark matter search.

The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L.

Toddlers' use of force against familiar peers: a precursor of serious aggression?

Possible precursors of serious aggression were identified in toddlers' use of force against peers. Instances of grabbing objects and hitting peers were recorded in a sample of 66 British 18- to 30-month-olds, observed at home with familiar peers and seen again 6 months later. Mothers rated aggressiveness in the context of other personality traits.

Kaposi sarcoma of major salivary gland origin: A clinicopathologic series of six cases.

Background: Kaposi sarcoma (KS), one of the defining tumors of acquired immune deficiency syndrome (AIDS), is rarely identified in the major salivary glands. To the authors' knowledge, no previous published series has evaluated the clinicopathologic aspects of this tumor in major salivary glands.

Methods: Six cases of salivary gland KS, diagnosed between 1970 and 1998, were retrieved from the files of the Oral and Maxillofacial Pathology Registry of the Armed Forces Institute of Pathology.

Effects of qualities of early institutional care on cognitive attainment. E.R.A. Study Team. English and Romanian Adoptees.

The adoption of children reared in poor quality Romanian institutions provided a "natural experiment" to determine whether psychological privation is the cause of later deficits. Low IQ at six years was strongly related to the duration of institutional care, with malnutrition having a weaker effect. After taking both into account, there was an additional effect of a particularly marked lack of individualized care.

Alveolar soft part sarcoma of the tongue: report of an unusual pattern in a child.

A case of an unusual, primary alveolar soft part sarcoma of the tongue in a 3-year-old boy is presented. Alveolar soft part sarcoma is a rare malignant tumor that presents more frequently in the head and neck region of infants and children. To date, only six cases of lingual alveolar soft part sarcoma presenting in the first decade of life have been reported in the English literature.

Prosocial action in very early childhood.

We tested a model of prosocial development, which predicted that prosocial action might decline, not increase, throughout childhood, becoming increasingly selective, individual, gender-related, and linked to emotional dysregulation. Sixty-six focal children at 18, 24, or 30 months of age were observed at home with familiar peers and then again 6 months later. Episodes of peer interaction were analysed for instances of sharing.

P53 and cyclin D1 staining patterns of malignant and premalignant oral lesions in age-dependent populations.

Objective: Recent epidemiologic studies have identified a trend of increasing cancer incidence in younger patients. The purpose of this study was to determine whether this might be reflected by different molecular mechanisms for tumor development.

Study Design: Dysplastic and malignant oral lesions from age-distinct patient populations were immunohistochemically analyzed for expression of p53 and cyclin D1.

Aggressive (malignant) epithelial odontogenic ghost cell tumor.

A 57-year-old man had an expanding cystic lesion of the anterior maxilla that demonstrated destruction and disruption of local structures. A cystic odontogenic neoplasm as well as various forms of odontogenic carcinoma was suspected. Incisional biopsy and microscopic examination revealed an aggressive epithelial odontogenic tumor with histologic features suggesting malignant transformation from an odontogenic cyst.

Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases.

Background: Polymorphous low grade adenocarcinomas (PLGA) are minor salivary gland neoplasms with a predilection for intraoral sites.

Methods: One hundred sixty-four cases of PLGA diagnosed between 1970-1994 were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Histologic features were reviewed, immunohistochemical studies and prognostic markers were performed, and patient follow-up was obtained.

Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA) Study Team.

Six per cent of child in a sample of 111 children who were adopted into U.K. families from Romania, and who were systematically assessed at the ages of 4 and 6 years, showed autistic-like patterns of behaviour.

Administration of n-3 fatty acids in the diets of rats or directly to hepatocyte cultures results in different effects on hepatocellular ApoB metabolism and secretion.

Hepatocytes derived either from rats fed a diet enriched in n-3 fatty acids or from rats fed a low-fat diet and cultured with an n-3 fatty acid (eicosapentaenoic acid, EPA) in vitro were used to distinguish between the dietary effects and the direct effects of n-3 fatty acids on hepatocellular apolipoprotein (apo) B metabolism and secretion. ApoB-48 and apoB-100 synthesis, degradation, and secretion as large (d<1.006) and small (d>1.

Immunoglobulin-derived polypeptides enter the regulated secretory pathway in AtT-20 cells.

Constitutively secreted proteins have traditionally been believed to be excluded from the regulated secretory pathway. In this work we show that kappa light chain and Fc fragment, two markers of the constitutive pathway, are present in the regulated pathway in AtT-20 cells. They colocalize with the endogenous hormone ACTH and they exhibit stimulus-dependent secretion.

Tyrosine phosphorylation of selected secretory carrier membrane proteins, SCAMP1 and SCAMP3, and association with the EGF receptor.

Secretory carrier membrane proteins (SCAMPs) are ubiquitously expressed proteins of post-Golgi vesicles. In the presence of the tyrosine phosphatase inhibitor vanadate, or after overexpression in Chinese hamster ovary (CHO) cells, SCAMP1 and SCAMP3 are phosphorylated selectively on tyrosine residue(s). Phosphorylation is reversible after vanadate washout in situ or when isolated SCAMP3 is incubated with the recombinant tyrosine phosphatase PTP1B.

Protein secretion by rat parotid acinar cells. Pathways and regulation.

Protein secretion from rat parotid acinar cells occurs in both the absence and presence of secretory agonists. Release takes place by four pathways that are distinguished by combined examination of their timing following biosynthetic labeling, their relative composition of salivary proteins, and their sensitivity to secretagogue stimulation. Following pulse-labeling with a radioactive amino acid, two unstimulated export pathways are detected--a constitutive-like pathway that is coupled to maturation of secretory granules and the later unstimulated exocytosis of secretory granules.

Enhanced glycosylation and sulfation of secretory proteoglycans is coupled to the expression of a basic secretory protein.

We have used coexpression of a salivary basic proline-rich protein (PRP) along with a proline-rich proteoglycan (PRPg) in pituitary AtT-20 cells to examine the regulation of glycosaminoglycan (GAG) biosynthesis and the storage of these secretory products for regulated secretion. The basic PRP caused a dose-dependent increase in sulfation of PRPg and also increased the extent to which PRPg polypeptide backbones are modified by a GAG chain. The sulfation of an endogenous proteoglycan was similarly increased in the presence of basic PRP; however, other sulfated secretory products of AtT-20 cells were unaffected.

Three mammalian SCAMPs (secretory carrier membrane proteins) are highly related products of distinct genes having similar subcellular distributions.

The primary structures of three human forms of secretory carrier membrane proteins (SCAMPs) have been deduced from full-length clones isolated from a HeLa cell cDNA library and confirmed by a combination of comparison to expressed sequence tags, microsequencing of purified protein, and in vitro transcription and translation. The structures indicated that SCAMPs are highly related products of distinct genes, and that the sequence identity of an individual SCAMP between different mammalian species is almost complete. Analysis of the distribution of SCAMPs among different mammalian tissues and cells indicates parallel expression of polypeptides and cognate mRNAs, and indicates that the three SCAMPs are usually but not always expressed together.

Passive sorting in maturing granules of AtT-20 cells: the entry and exit of salivary amylase and proline-rich protein.

Previous studies have suggested that salivary amylase and proline-rich protein are sorted differently when expressed in AtT-20 cells (Castle, A.M., L.

Evidence for colocalization and interaction between 37 and 39 kDa isoforms of secretory carrier membrane proteins (SCAMPs).

Secretory carrier membrane proteins (SCAMPs) are proteins of post-Golgi recycling carriers, including regulated secretory organelles. The two major size variants, SCAMP1 (37 kDa) and SCAMP2 (39 kDa), extensively colocalize in membranes of fibroblasts and parotid acinar cells based on immunocytochemistry and velocity centrifugation, although the relative amounts of each variant may differ in selected organelles. SCAMP1, and to a lesser extent, SCAMP2, are substrates for chemical crosslinking in situ, and the recognizable crosslinking products of SCAMP1 suggest potential formation of homomultimers.

Infant nutrition: implication for somatic growth, adult onset diseases, and oral health.

The gold standard for assessing the adequacy of nutrient intake in pediatrics is that diet which promotes optimal growth and development. Thus, it is crucial that our methods for measuring these outcomes be valid, reliable, and widely accepted. A review of the recent medical literature in the field of clinical nutrition indicates that both growth data and dietary standards continue to evolve as more data accrue concerning their applicability in both health and disease.

Two regulated secretory pathways for newly synthesized parotid salivary proteins are distinguished by doses of secretagogues.

Low doses of the muscarinic agonist pilocarpine (0.1-1 microM) and the beta-adrenergic agonist isoproterenol (0.5-4 nM) stimulate a minor regulated secretory pathway for salivary proteins in rat parotid lobules.

The unique proline-rich domain of parotid proline-rich proteins functions in secretory sorting.

When expressed in pituitary AtT-20 cells, parotid proline-rich proteins enter the regulated pathway. Because the short N-terminal domain of a basic proline-rich protein is necessary for efficient export from the ER, it has not been possible to evaluate the role of this polypeptide segment as a sorting signal for regulated secretion. We now show that addition of the six-amino acid propeptide of proparathyroid hormone to the proline-rich protein, and especially to a deletion mutant lacking the N-terminal domain, dramatically accelerates intracellular transport of these polypeptides.