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Biomedical subjects

L S Cutler

Publications and source records attributed to L S Cutler.

At least 55 records · Page 3Linked to original sources

An electrophysiological study of the postnatal development of the autonomic innervation of the rat submandibular salivary gland.

The development of the functional relationship between the autonomic nerves that regulate secretion and the acini of the gland (SMG) was studied. Electrophysiologic studies indicated that stimulation of the parasympathetic nerves at birth caused the secretion of fluid from the duct system but did not cause protein secretion from the developing acini or terminal tubules. Stimulation of the sympathetic innervation (superior cervical ganglion) did not cause protein secretion from developing acini or terminal tubules until 5 days after birth. The amount of protein released progressively increased in response to electrical stimulation of the cervical ganglion as the animals aged. This increased secretory response was correlated with the appearance of increasing numbers of catecholamine-containing neurones in the gland parenchyma.

Animals↗

Inhibition of rat salivary gland adenylate cyclase by glycosaminoglycans and high molecular weight polyanions.

The effects of hyaluronic acid, chondroitin-4 and -6 sulphate, dermatan sulphate, heparin and the sulphated, polysugar dextran sulphate on membrane-associated adenylate cyclase were investigated in a plasma-membrane fraction derived from the glands. Adenylate-cyclase activity was inhibited in a dose-dependent fashion by all. The potency (concentration causing a 50 per cent inhibition (Ki) of adenylate cyclase activity) of each molecule varied with the degree of sulphation of the agent tested. The GTP and Gpp(NH)p activation of adenylate cyclase as well as basal-enzyme activity and of adenylate cyclase by isoproterenol (a beta-adrenergic agonist) were inhibited; however, little effect on hormone binding (assessed by [3H]-dihydroalprenolol binding) was observed at Ki concentrations. Inhibition of NaF-activation of adenylate cyclase was not as pronounced as the other inhibitory effects. The findings suggested that the agents inhibited enzyme activity by action at or near the catalytic site; hence the effect of these molecules on forskolin activation of adenylate cyclase was investigated. The polyanions inhibited forskolin stimulation of the enzyme to the same degree that they had previously inhibited basal, GTP and hormonally-stimulated enzyme activity. Thus, these molecules inhibited adenylate cyclase by an action (perhaps charge-related) that directly effected the stabilization of catalytic site of the enzyme. Thus polyanions of the type tested can directly modulate adenylate-cyclase activity and may serve as potential regulatory molecules for various biologic functions which are cyclic-AMP dependent.

Adenylyl Cyclase Inhibitors↗

Glycogen-rich tumor of the oral minor salivary glands. A histochemical and ultrastructural study.

A detailed electronmicroscopic study on glycogen-rich tumor is presented. The neoplasm originated from the minor salivary glands on the ventral surface of the tongue. The role of myoepithelial cells in the histogenesis of this lesion is not supported. It is proposed that the tumor arises from "undifferentiated" stem cells analogous to cells in the "end bud" stage of salivary gland morphogenesis. The presence of a large amount of glycogen is secondary to defective carbohydrate metabolism within the tumor cells.

Adenoma↗

Monomorphic adenomas of the parotid glands. Their ultrastructure and histogenesis.

Three cases of monomorphic basal cell adenoma of the parotid glands were studied with light microscopy. In one patient, fresh tissue was available for electron microscopic observations. On the basis of ultrastructural findings it was concluded that myoepithelial cells play little, if any, role in the histogenesis of this lesion. The tumor originates from the undifferentiated stem cells analogous to the cells seen at the "end bud" stage of salivary gland morphogenesis prior to their further cytodifferentiation and functional maturation into secretory and myoepithelial cells. In fully developed salivary glands such undifferentiated stem cells reside as "reserve" cells in the intercalated ductal system.

Adenoma↗

Ultrastructure of monomorphic adenoma (ductal type) of the minor salivary glands.

A monomorphic adenoma (ductal type) of the palatal minor salivary glands is reported. Ultrastructurally, the predominant tumor cells contained zymogenlike dense secretory granules. There was a continuum from tumor cells with little or no secretory granules to ones with increasing numbers of granules. Except for that, the tumor cells shared many of their fine structural features. Histogenetically, the tumor originated from neoplastic proliferations of "undifferentiated" stem cells corresponding to "end-bud" stage of salivary glands embryogenesis. Under neoplastic influences, such cells underwent further cytodifferentiation and functional maturation along the secretory cell lines. In mature salivary glands, such pluripotential cells reside as "reserve" cells in the intercalated ducts.

Adenoma↗

An electron-microscopic and cytochemical study of follicular ameloblastoma.

The ultrastructural and enzyme cytochemical features of two follicular ameloblastomas were investigated. The peripheral cells of the follicular areas in both lesions had several types of tall columnar cells which were highly polarized and showed varying degrees of cellular differentiation. These polarized cells had their nuclei situated away from the basal lamina, and often contained dilated strands of endoplasmic reticulum in the subnuclear cytoplasm. Some of these cells also contained dense-cored secretory granules, condensing granules and coated vesicles in the cytoplasm adjacent to the basal plasma membrane. These cells bore a striking resemblance to pre-ameloblasts and early secretory ameloblasts. Alkaline phosphatase and ATPase cytochemistry supported these morphologic observations. Interestingly, the central cells of the follicular areas were consistently negative for alkaline phosphatase activity as were the peripheral cells, while both cell types had ATPase activity demonstrable at their cell surface.

Acid Anhydride Hydrolases↗

Cytochemical methods for the localization of adenylate cyclase. A review and evaluation of the efficacy of the procedures.

The cytochemical procedures for localizing adenylate cyclase have been a source of controversy since their introduction. The importance of cyclic adenosine monophosphate (AMP), the product of adenylate cyclase's action on adenosine triphosphate (ATP), in cell biology is clear. Thus, the ability to localize this enzyme system reliably is an important tool in the study of various cellular functions. This report reviews the literature and presents a biochemical evaluation of the methods for localizing adenylate cyclase. The review and data presented serve to clarify many of the controversies surrounding this important cytochemical procedure. It is evident that although there are problems associated with localizing the enzyme, several valid procedures are currently available for the cytochemical localization of adenylate cyclase. In using these procedures, the effects of fixation and the capture agent on adenylate cyclase activity in the particular tissue being studied should be considered. Only repurified adenylyl imidodiphosphate [App(NH)p] should be used in the incubation medium. If care is taken, the use of these techniques can be of great value in the continued study of the role of cyclic nucleotides in cell biology.

Adenylyl Cyclases↗

Prenatal and postnatal histogenesis of myoepithelium in hamster submandibular gland. An ultrastructural study.

Prenatal and postnatal development of myoepithelium in the hamster submandibular gland has been studied by electronmicroscopy. Myoepithelial cells originate from 'undifferentiated' stem cells in the epithelial anlage at 14-1/2 days of gestation. At this stage of their cytodifferentiation, the myoepithelial cells are recognizable by their elongated shape, peripheral location between the basal lamina and other epithelial cells in the anlage, axially oriented dense nucleus and low density cytoplasm. The myofilament deposition starts at birth, initially in the basal cytoplasm. With advancing maturation, there is a progressive increase in the number of myofilaments and in two week-old animals they virtually fill the cytoplasm. The mature myoepithelial cells are characterized by their shape, location, cytoplasmic myofilaments which run parallel to the basal lamina and display focal densities along their course, hemidesmosomes and pinocytotic vesicles. The morphologic evidence supports their epithelial origin but militates against their ability to mediate the synthesis of fibrous, mucinous, chondroid or osseous material as proposed by others (Grishman, 1952; Azzopardi and Smith, 1959; Doyle et al., 1968; Hubner et al., 1971).

Epithelium↗

Myoepithelial cell adenoma of the parotid gland: a light and ultrastructural study.

Light, histochemical, and ultrastructural features of a myoepithelial cell adenoma of the parotid gland are described. Ultrastructurally, the neoplasm was almost entirely composed of myoepithelium. The spindle-shaped myoepithelial cells and their processes were filled with longitudinally oriented myofilaments with characteristic densities along their course and marginal attachment plaques. The tumor cells were interconnected by desmosomes. The role of myoepithelium in the genesis of some salivary gland tumors is discussed.

Adenoma↗

Ultrastructural localization of salivary acidic proline-rich proteins from Macaca fascicularis.

Using an indirect immunoferritin method, the subcellular distribution of acidic proline-rich proteins (MPRP) in the acinar cells of the macaque parotid and submandibular glands was defined. MPRP was found in the "spherule" substructure of the secretory granules as well as in specific Golgi transfer vesicles and in vesicles budding from the Golgi apparatus. The data suggest that the acidic proline-rich proteins of the primate Macaca fascicularis are synthesized and packaged by conventional exocrine mechanisms. In addition, these proteins appear to be packaged and transferred to the secretory granules of parotid and submandibular gland acinar cells as discrete aggregates that remain as a separate "spherule" area in the secretory granules.

Animals↗

Melanotic neuroectodermal tumor of infancy: an ultrastructural study, literature review, and reevaluation.

Two cases of melanotic neuroectodermal tumor of infancy were examined by electron microscopy and an extensive review of the literature was performed. Ultrastructural examination revealed several features not previously described for this lesion. Three different types of melanin granule formation were observed, many cells had a single cilium, and cell junctions of the "close" or "modified-tight" type were seen, but no desmosomes were found. The morphologic data were consistent with the concept that the tumor arises from neural crest cells. The review of the literature indicated that there have been 158 reported cases of this lesion, including the two reported here. There were five cases of malignant tumor reported for a rate of 3.2%. This rate of malignancy is very high in view of the fact that the tumor has been described as universally benign. The significance of this finding is discussed with regard to melanin-producing lesions of the oral cavity.

Female↗

Effects of reserpine treatment on beta-adrenergic/adenylate cyclase modulate secretion and resynthesis by the rat submandibular gland.

Chronic reserpine (adrenergic blocking) treatment causes a marked accumulation of secretory protein in the rat submandibular gland (SMG) but discharge of this material is delayed in response to isoproterenol stimulation. The purposes of this study were to investigate the effects of chronic reserpine treatment on 1) the number of beta-adrenergic receptor. 2) the sensitivity of cell-surface-associated adenylate cyclase to various concentrations of isoproterenol, and 3) to correlate these data to morphologic studies of the secretion and resynthesis phases of the isoproterenol-induced secretory cycle in the rat SMG. Animals were injected with reserpine (0.5 microgram/g b.w.) for 6 days. Plasma membrane fractions were prepared. The adenylate cyclase response to a series of isoproterenol concentrations, and the number of beta-adrenergic receptors ([3H]-alprenolol binding) were determined. Other animals were given a single dose of isoproterenol (0.8 mg/100 g b.w.) and the SMG was examined by light and electron microscopy at various times (30 min to 24 h) after treatment. Chronic reserpine treatment leads to a 2.5-fold increase in SMG beta-adrenergic binding sites and a 50-fold increase in adenylate cyclase sensitivity to IPR stimulation when compared to controls. However, secretion and resynthesis of secretory product in response to IPR stimulation was greatly delayed in reserpinized rats.

Adenylyl Cyclases↗

Cytochemical evidence for the segregation of adenylate cyclase, Ca2+-, Mg2+-ATPase, K+-dependent p-nitrophenyl phosphatase in separate membrane compartments in human platelets.

The blood platelet has three morphologically distinct membrane systems. In addition to the plasma membrane the platelet has an 'open canalicular system' (surface-connected intracytoplasmic membrane system) and a microsome-like 'dense tubular system'. The open canalicular and dense tubular systems have been implicated in Ca2+ transport, cyclic nucleotide (cAMP) synthesis and prostaglandin and thromboxane synthesis. Precise definition of the function of the different membrane systems requires analysis of their unique chemical activities. Broken cell preparations are used to advantage for such studies. However, clean separation and definition of the origin and composition of the membrane fractions has been difficult because well-defined marker enzymes for the various membrane systems have not been conclusively established. Platelets were fixed for 5 min in 1% paraformaldehyde-0.2% glutaraldehyde and assayed for K+-dependent p-nitrophenyl phosphatase, Ca2+-, Mg2+-ATPase and adenylate cyclase K+-dependent p-nitrophenyl phosphatase was localized only at the plasma membrane while Ca2+-, Mg2+-ATPase and adenylate cyclase were found relatively segregated to the open canalicular and dense tubular systems. The segregation of these enzymes to separate membrane compartments may have significant implications with regard to understanding platelet function.

4-Nitrophenylphosphatase↗

The dependent and independent relationships between cytodifferentiation and morphogenesis in developing salivary gland secretory cells.

The mesenchymal capsule was removed from the epithelial anlage of 15 days (unbranched) and 16 day (initially branched) fetal rat submandibular gland (SMG) rudiments. The undifferentiated epithelial portion of the SMG rudiments was placed in tissue culture and examined by light and electron microscopy and histochemistry for secretory peroxidase. The 15 day fetal SMG epithelial rudiments failed to attach, and spread over the culture dish and degenerated by 3 days in culture. The 16 day epithelial rudiments attached to the dish and the cells spread radially from the explant. Mitotic activity was minimal. Cells spreading from the 16 day rudiments underwent cytodifferentiation, giving rise to two secretory cell types: 1) peroxidase containing "proacinar cells," and 2) secretory "terminal tubule" cells. The results suggest that in the developing SMG, morphogenesis and cytodifferentiation are partially coupled but independently regulated processes. The earliest phases of morphogenesis (rudiment down growth and primary branching) seem to be required to initiate cytodifferentiation. Once initiated, cytodifferentiation can proceed in the continued morphogenesis (tissue organization) or significant amounts of connective tissue elements.

Animals↗

Cytochemical localization of adenylate cyclase.

This study examined 1) the effect of lead and fixation on adenylate cyclase activity, 2) the effect of lead on App(NH)p, and 3) the specificity of App(NH)p as a substrate for adenylate cyclase under the conditions of the cytochemical assay. The results indicated that: 1) fixation that provides adequate structural preservation inhibits enzyme activity to varying degrees depending on the tissue, fixative, length and temperature of fixation; 2) millimolar concentrations of lead do not negatively affect the adenylate cyclase activity of several different tissues (especially if 10 mM NaF is present); 3) lead does not cause the nonenzymatic hydrolysis of App(NH)p; 4) the App(NH)p obtained from the supplier is contaminated and should be purified before use, since lead can interact with the contaminants and this may be a source of error in the assay; and 5) adenylate cyclase appears to be the major enzyme that cleaves App(NH)p under cytochemical conditions.

Adenylyl Cyclases↗

Cytochemical localization of ouabain-sensitive (K+)-dependent p-nitrophenyl phosphatase (transport ATPase) in human blood platelets.

The ultrastructural cytochemical localization of a potassium-dependent oubain-sensitive nitrophenyl phosphatase (transport ATPase) activity in human blood platelets is described. This potassium-dependent nitrophenyl phosphatase activity was not affected by 5 mM levamisole, indicating that the reaction product identified was not due to nonspecific alkaline phosphatase activity. The K+-dependent nitrophenyl phosphatase was strictly localized to the platelet plasma membrane, while the open canalicular system and dense tubular system were devoid of reaction product. In contrast, (Ca2+,Mg2+)-activated ATPase activity was predominantly localized in the open canalicular system and dense tubular system with very little cytochemical activity expressed at the plasma membrane. These data demonstrate a relative segregation of these enzymes into unique membrane compartments of the human platelet. Such data may be useful with regard to identification of purified membrane fractions from platelets and may be significant with regard to the understanding of the function(s) of the different membrane compartments of the human platelet.

4-Nitrophenylphosphatase↗