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Biomedical subjects

L S Cutler

Publications and source records attributed to L S Cutler.

18 recordsLinked to original sources

Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus.

Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.

Animals

Adenylate cyclase in muscular dystrophy.

The purpose of this study was to determine whether the previously reported differences in adenylate cyclase activity between the sarcolemma of normal and dystrophic chick muscles are also found in the SR, to search for a possible relationship between the adenylate cyclase changes and the pathophysiology of dystrophy, and to investigate whether the findings can be extended to Duchenne human muscular dystrophy by studying the adenylate cyclase and ATPase activities of erythrocyte ghosts from DMD patients and carriers. Microsomes were separated by standard techniques from the pectoralis muscles of normal and dystrophic ckeckens of various ages. The microsomal yields were significantly larger in dystrophic muscles. Adenylate cyclase activities in dystrophic microsomes were higher than those in matched controls and increased with the progression of the disease. The ratio between the two rose from one at 2 weeks of age to nine at about 9--10 weeks. Kinetic analyses showed that the ks for MgATP2- was about 40 microM (at 3 mM Mg2+ and 0.3 mM Ca2+) both in normal and dystrophic microsomes, that calcium caused umcompetitive inhibition of the enzyme (Ki = 0.2 mM), that the effect of calcium was noncooperative (Hill coefficient, nH = 1), that calcium did not affect the cooperativity for MgATP2-, and that magnesium competitively removed the calcium inhibition and caused additional, cooperative stimulation of the enzymatic activity (ka = 1.5 mM; NH =2). The major difference between normal and dystrophic adenylate cyclase was a higher enzymatic velocity in the latter, suggesting a larger amount of enzyme. We investigated whether altered cAMP levels may effect calcium accumulation. Calcium uptake measured (in the presence of oxalate) at several ages revealed no difference between normal and dystrophic chickens. The extent of calcium binding was also similar, although the kd for Ca2+ was lower in dystrophic microsomes. Binding was enhanced in the presence of exogenous protein kinase, but the responses of normal and dystrophic tissues were similar. We concluded that the elevation of adenylate cyclase in dystrophy was not related to microsomal calcium accumultion. Ivestigation of the localization of microsomal adenylate cyclase supported this view. Separation of calcium-loaded microsomes on a discontinuous sucrose gradient into four fractions demonstrated that adenylate cyclase activity, measured in the presence of Lubrol-PX and EGTA, was inversely related to calcium-accumulating activity. Na+, K+-ATPase comigrated with adenylate cyclase. Highest specific activities were found in the lightest fraction. These observations were confirmed by histochemical studies. The reaction product from adenylate cyclase activity was present predominantly in the terminal cisternae of the SR. In the context of the literature, our findings suggest that the rises in adenylate cyclase and Na+, K+-ATPase in avian dystrophy are compensatory changes, elicited by a defect in ECC at the calcium release step...

Adenylyl Cyclases

Effects of low-level X-radiation on 7,12-dimethylbenz[a]anthracene-induced lingual tumors in Syrian golden hamsters.

The effects of repeated low-dose-rate, high-dose-rate X-radiation of the head and neck on lingual tumor induction by 7,12-dimethylbenz[a]anthracene (DMBA) in Syrian golden hamsters were studied. Animals received either topical application as 0.5% DMBA in acetone on the lateral middle third of the tongue three times a week for 15 consecutive weeks, 20-R X-radiation exposures of the head and neck once a week for 15 consecutive weeks, or concurrent radiation and DMBA treatments for 15 consecutive weeks. Animals were examined visually at regular intervals, and all were killed 35 weeks after the start of treatments. All tissues were than examined histopathologically. Animals receiving radiation alone had no detectable changes. Animals receiving DMBA plus radiation had an excess of papillomas compared to animals receiving only DMBA (35% vs. 15%). In addition, an excess of nonlingual oral tumors (lip, gingiva, and floor of mouth) was found in DMBA-treated plus radiation-treated animals versus DMBA-treated animals. These results suggest that repeated, localized, low-level X-radiation exposures enhance chemical tumorigenesis in a variety of oral tissues of Syrian golden hamsters.

9,10-Dimethyl-1,2-benzanthracene

Developmental distribution of microperoxisomes in the rat submandibular gland.

The present study investigated the size, number, and distribution of microperoxisomes (MP) during the prenatal and postnatal development of the rat submandibular gland (SMG). A three-fold increase in MP number per cell was observed in the cells of the rudiment from the 15th to the 16th day of gestation. The early secretory and striated duct cells contained about 9.0 MP. The number of MP per secretory cell decreased such that 3.5 MP were found in each mature acinar cell. In the striated duct cells, MP number progressively increased to 40.0. As the convoluted granular tubule cells (CGT) developed from striated duct cells there was an increase in MP number from 16.0 to 26.0/cell. At maturity, the convoluted granular tubule cells contained only 14.0 MP. Throughout development of the SMG, intercalated duct cells showed only rare MP. The data suggests that the number, size, and distribution of MP changes as a function of the particular path of differentiation followed by the various cells in the rat SMG.

Animals

Phosphatase enzymes. Cytochemical study of pleomorphic adenoma and normal human salivary glands.

Human parotid glands, submandibular glands, and pleomorphic adenomas were examined by electron microscopic histochemistry. All epithelial cells of the normal salivary glands showed plasma membrane adenosine triphosphatase (ATPase) and inosine diphosphatase (IDPase) activity. However, myoepithelial cells reacted most intensely. Pleomorphic adenomas showed epithelial cells within solid and ductal portions of the tumors that were variably reactive for both ATPase and IDPase. Histochemical examination of the epithelial cells in the myxoid portions of the tumors did not provide conclusive evidence as to the nature of their progenitor cells. Surface-associated phosphatases (alkaline phosphatase, ATPase, and IDPase) cannot be reliably used as histochemical markers of salivary gland myoepithelial cells. Therefore, morphological and phosphatase histochemical studies that intend to examine the role of myoepithelial cells in salivary gland neoplasms must be interpreted with care.

Acid Anhydride Hydrolases

An ultrastructural study of eosinophilic granuloma: the Langerhans cell--its role in histogenesis and diagnosis.

An electron microscopic study of a case of eosinophilic granuloma of the mandible was performed. The fine structural similarity between the "histiocytic" cells of the lesion and epidermal Langerhans cells is discussed with regard to current theories and information on the origin of Langerhans cells and their potential role in the histogenesis of eosinophilic granuloma and other variants of histiocytosis X.

Adult

Membrane changes during cartilage maturation. Increase in 5'-nucleotidase and decrease in adenosine inhibition of adenylate cyclase.

To examine the potential participation of the plasma membrane in differentiation, we studied the enzymatic activities of 5'-nucleotidase and adenylate cyclase as a function of chondrocyte maturation. 16-day-old chick embryo tibiae epiphyses were dissected into proliferative, growing and hypertrophying zones. Partially purified membrane fractions prepared by differential centrifugation from the respective tissue segments were assayed for enzymatic activity. Cell suspensions from the same segments were examined cytochemically for the presence of 5'-nucleotidase. The findings show that the 5'-nucleotidase activity of the chick embryo epiphyseal cartilage has the following characteristics: (a) it has a Km of about 25 muM for 5'AMP, and is inhibited by a mixture of 2' and 3'AMP (apparent Ki about 10(-4) M) and by AOPCP; (b) it is predominantly localized at the cell surface but is also detected in the cytoplasm and in association with nuclear heterochromatin; and (c) it increases 10-fold (on a DNA basis) during the maturation of the epiphyseal cartilage cells. The adenylate cyclase activity has these characteristics: (a) it does not change during chondrocyte maturation (on a DNA basis); (b) its susceptibility to adenosine inhibition decreases at least 10-fold. The implication of these findings relative to a possible role of adenosine in cellular communication is discussed.

Adenosine

Concurrent cytochemical localization of adenylate cyclase and peroxidase in the developing rat submandibular gland.

An electron microscopic histochemical technique for the concurrent localization of adenylate cyclase and endogenous peroxidase is described. The procedure involves incubation of glutaraldehyde fixed tissue in adenylate cyclase medium followed by washing and incubation in 3,3'-diaminobenzidine tetrahydrochloride medium to demonstrate peroxidase activity. Adenylate cyclase was localized at the cell surface of the tissue investigated (20 day fetal rat submandibular gland) while peroxidase was localized in the rough endoplasmic reticulum and secretory granules of some cells. Biochemical and histochemical controls indicate that the procedure is valid. The potential use of this procedure and variations of the procedure are discussed.

Adenylyl Cyclases

Ultrastructure of the parotid duct. Cytochemical studies of the striated duct and papillary cystadenoma lymphomatosum of the human parotid gland.

To our knowledge, there are currently no reports in the literature that discuss the fine structure of the striated ducts of the human parotid gland. Papillary cystadenoma lymphomatosum (Warthin's tumor) is a benigh neoplasm found almost exclusively in the parotid gland that represents about 16% of all neoplasms of the gland. This neoplasm is believed to arise from the striated and/or excretory ducts, but there are contradictions with regard to the proposed origin and the cellular composition of some Warthin's tumors. Tissue was obtained at the time of surgery and examined ultrastructurally and cytochemically for the localization of alkaline phosphatase and adenosine triphosphatase. Myoepithelial cells were found ultrastructurally and cytochemically on the proximal aspect of the striated duct, with their cell bodies situated at the junction of the striated and intercalated ducts. Two Warthin's tumors were observed with cells that were structurally and cytochemically similar to myoepithelial cells.

Adenosine Triphosphatases

Ultrastructural localization of membrane phosphatases in teratocarcinoma and early embryos.

Ectodermal cells of the two- and three-germ layer-thick mouse egg-cylinders are considered to be the progenitors of embryonal carcinoma cells in embryo-derived teratocarcinomas. In an attempt to find differences between the tumor cells and equivalent embryonic cells, we have studied the electron microscopic cytochemical localization of alkaline phosphatase, 5'-nucleotidase, and Mg2+-activated adenosine triphosphatase (ATPase) in embryo-derived teratocarcinomas and mouse egg-cylinders. Alkaline phosphatase was detected in both embryonic and tumor cells, but its activity appeared much more intense in the tumor cells. No ATPase was demonstrated in embryonic ectodermal cells of 6-day-old embryos and only in occasional cells of 7- and 8-day-old embryos. No 5'-nucleotidase activity could be demonstrated in 6- to 8-day-old cylinders. There was marked ATPase and 5'-nucleotidase activity in the membranes of embryonal carcinoma cells. These data point out some differences on the plasma membrane between the embryonal carcinoma cells and equivalent embryonic cells. The potential significance of these differences is discussed with regards to the transformation of embryonic cells in tumor cells. (Am J Pathol 87:297-310, 1977).

Adenosine Triphosphatases

Intercellular contacts at the epithelial-mesenchymal interface of the developing rat submandibular gland in vitro.

An ultrastructural study of the development of the rat submandibular gland (SMG) analage in vitro was undertaken to determine if epithelial-mesenchymal and epithelial-nerve contacts were integral events in the differentiation of the gland in vitro as they are in vivo. SMG rudiments were removed at the stalk-bulb stage (15 days in utero) and cultured for 6 days on a millipore filter in supplemented McCoy's 5A media. Rudiments were taken at daily intervals, fixed and processed for electron microscopy. The overall development of the explanted rudiments closely paralleled their maturation in vivo although cultured glands lagged 24-36 h behind their normal counterparts. Direct epithelial-mesenchymal contacts were seen after the morphogenetic patterning of the gland had been established but prior to functional differentiation of the rudiment. Epithelial-nerve contacts were not seen although healthy axons were seen in the stroma throughout the culture period. The study indicates that epithelial-nerve contacts are probably not required for morphogenesis of cytodifferentiation of the rat SMG. However, direct epithelial-mesenchymal contacts appear to be an integral part of the developmental sequence of the rat SMG.

Animals

Warthin's tumor. Report of a case and survey of 205 salivary neoplasms.

A case of Warthin's tumor with an unusual sialographic appearance is reported. The extensive pooling of the contrast media within the tumor was probably the result of communication of the cystic spaces of the tumor with the ductal system of the parotid gland. This case stimulated a re-examination of the incidence of this tumor, with a study of 205 major salivary gland tumors from pathology reports in the files of Hartford Hospital which is affiliated with the University of Connecticut Health Center in Farmington, Connecticut.

Adenolymphoma

Biochemical and cytochemical studies on adenylate cyclase activity in the developing rat submandibular gland: differentiation of of the acinar secretory compartment.

To investigate membrane changes in development of the exocrine cells of the rat submandibular gland (SMG), biochemical and cytochemical studies of adenylate cyclase activity were performed on prenatal and postnatal glands. SMG rudiments and glands were studied from 15 days of gestation op to birth and 1, 2, 3, 4 and 24 weeks after birth. Glands were chemically assayed for adenylate cyclase activity using the procedures of Salomon and coworkers and cytochemically studied using a procedure which was verified biochemically. At 15-16 days of gestation basal adenylate cyclase activity was low and no staining could be observed. Adenylate cyclase activity rose six-fold from the 16th to the 18th day of gestation. Adenylate cyclase staining became evident along the surface of most of the cells of the rudiment at this time. Basal adenylate cyclase activity remained relatively constant from the 18th day of gestation up to 24 weeks of age. However, sequential changes were seen in the cytochemical localization, especially in relation to the apical plasma membrane of the developing secretory cells.

Adenylyl Cyclases

Repression and autogenous stimulation in vitro by bacteriophage lambda repressor.

Purified lambda repressor protein is shown to reduce the lambda DNA-directed synthesis of proteins in vitro as determined both by net amino-acid incorporation and by analysis of specific lambda-coded proteins resolved by sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis. By means of different lambda DNA templates carrying deletion and point mutations in the operators o-L or o-R, it has been possible to demonstrate repression of the synthesis of two classes of lambda proteins. The synthesis of one, class c, appears to be controlled from the operator o-L and is more efficiently repressed at low concentrations of the repressor than that of the other class of repressible lambda proteins, class d, which is controlled from the operator o-R. Several other proteins synthesized in vitro are not repressible. Some of these are coded by the J-att region. In addition, the repressor appears to have another activity, that of stimulating the synthesis of a protein identified as the repressor itself. Lambda repressor appears to stimulate its own synthesis by acting at prm, a site defined by the cis-acting mutation prm 116.

Chromosome Mapping

Effect of alpha, alpha'-dipyridyl on the basement membrane of tooth germs in vitro.

Dipyridyl inhibits the morphogenesis of tooth germs, but the germs recover when transferred to control medium. In this study, the effect of dipyridyl on basement membrane was investigated in vitro. The basal lamina was always present, but the subjacent collagen fibrils disappeared in the presence of dipyridyl and reappeared during recovery in control medium.

2,2'-Dipyridyl