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L S Cutler

Publications and source records attributed to L S Cutler.

At least 19 recordsLinked to original sources
PubMed1992

The correlation of temporal regulation of glycosaminoglycan synthesis with morphogenetic events in mouse tooth development.

The purpose of this study was to investigate the pattern of sulphated glycosaminoglycan synthesis during morphogenesis and cytodifferentiation in mouse tooth rudiments and to compare the results with those obtained in another study for salivary gland, a branched organ. Sulphated glycosaminoglycan was labelled by incubating molar rudiments from day 15 of gestation to day 1 post partum in medium containing [35S]-sodium sulphate. The rudiments were washed, homogenized and digested in pronase and then were sequentially digested by chondroitinase ABC and chemically degraded by nitrous acid oxidation. The fractions from each of these procedures were analysed by chromatography on Sephadex G-50 columns. The analysis revealed that, during morphogenesis, levels of chondroitin sulphate increased to a peak of 91% at day 18 and levels of heparan sulphate diminished to 8% during this period. As cytodifferentiation occurred, the level of chondroitin sulphate dropped to 64% and that of heparan sulphate increased to 35%. These results are similar to those reported for rat submaxillary gland, a branching organ. It appears that this pattern of sulphated glycosaminoglycan synthesis is not a unique feature of branching morphogenesis but may be one which marks the transition between morphogenesis and cytodifferentiation in non-branching rudiments as well.

Animals↗
PubMed1991

Immunocytochemical localization of heparan sulphate proteoglycan in the rat submandibular gland.

Heparan sulphate proteoglycan is the predominant proteoglycan synthesized by the parenchymal cells of the rat submandibular gland. A polyclonal antibody was used to localize this proteoglycan in the adult rat submandibular gland. Localization was accomplished by indirect immunoperoxidase cytochemistry at the light and electron microscopic levels. Heparan sulphate proteoglycan was localized in a continuous, linear pattern in the lamina densa of the basement membrane surrounding all of the epithelial components of the gland as well as the basement membrane of the capillaries and small arterioles in the glandular stroma. In addition, heparan sulphate proteoglycan was seen in vesicles and pits along the acinar cell basal plasmalemma adjacent to the basement membrane and in the endoplasmic reticulum and Golgi apparatus of the acinar cells.

Animals↗
PubMed1991

Sulphated glycosaminoglycan synthesis by developing rat submandibular gland secretory units.

This study examined the profile of S-GAGs synthesized by presecretory and secretory units isolated from rats at 17, 18 and 21 days in utero and 1, 6 and 35 days after birth. The units were incubated for 2 h in medium containing [35S]-sodium sulphate and then processed and analysed. Secretory units from 17-day embryonic presecretory units produced a S-GAG profile composed of approx. 73% chondroitin sulphate and 26% heparan sulphate. When cells of the embryonic units undergo cytodifferentiation to become secretory cells (18 days in utero), there is a major change in the relative amounts of S-GAG synthesized with 54% of the S-GAG produced being heparan sulphate and 41% chondroitin sulphate. There is a progressive increase in the relative amount of heparan sulphate produced and a concomitant decline in chondroitin sulphate as the secretory compartment of the gland matures. By 35 days after birth, the secretory units produced a S-GAG profile that was greater than 85% heparan sulphate and less than 10% chondroitin sulphate. The ratio of heparan sulphate/chondroitin sulphate production was 0.36 by 17-day embryonic presecretory units and shifted to 9.1 by 35-day postnatal units.

Animals↗
PubMed1991

Experimental autoallergic sialadenitis in the LEW rat. I. Parameters of disease induction.

Experimental autoallergic sialadenitis (EAS) is an autoimmune mononuclear cell infiltration of the submandibular salivary gland that results in tissue destruction and glandular dysfunction. A previous report has described an animal model of induced EAS in LEW rats following sensitization with allogeneic WF submandibular gland (SMG). The present study extends this observation to an EAS disease model induced following sensitization of LEW rats with syngeneic LEW SMG. Furthermore, we describe the characterization of the mononuclear cells in the glandular infiltrates, evaluate the production of autoantibodies, and establish the parameters important for reproducible induction of EAS. Our results demonstrate that EAS can be induced in a completely syngeneic system and the histopathology of disease induction in the syngeneic and allogeneic model systems is similar. Helper/inducer (CD4+) and suppressor/cytotoxic (CD8+) T-cell subsets are the dominant cell types in the salivary mononuclear cell infiltrate. An anti-duct autoantibody was found in the serum of virtually all LEW rats with EAS. Although closely associated with disease development, the presence of this antibody was not a prerequisite for development of histopathologic disease. Induction of disease in both the syngeneic and allogeneic models of EAS is dependent upon administration of Bordetella pertussis at the time of sensitization. Finally, the histopathology of the cellular infiltrates in both the allogeneic and syngeneic models of EAS resemble those observed in the salivary tissues of Sjögren's patients. While there are several differences between EAS in the LEW rat and the full expression of Sjögren's syndrome, EAS may serve as a model to study the salivary gland component of this complex human disease.

Animals↗
PubMed1991

Experimental autoallergic sialadenitis in the LEW rat. II. Target antigens are associated with cell surface and intracellular particulate fractions derived from the submandibular gland.

Experimental autoallergic sialadenitis (EAS) in the LEW rat is an autoimmune lymphocytic destruction of the submandibular gland (SMG) induced by sensitization with an SMG homogenate emulsified in adjuvant. Here we report that the antigens in the SMG homogenate involved in the induction of EAS can be localized to both cell-surface and intracellular particulate fractions. Differential centrifugation procedures were used to isolate 10,000g, 25,000g, 40,000g, and 100,000g particulate fractions from the SMG of LEW or WF rats. The particulate SMG fractions were used to sensitize female LEW rats for EAS induction. Since the protein concentrations of the fractions varied as a percentage of their composition in the whole homogenate, additional experiments were performed using equivalent protein concentrations for sensitization. Two weeks after sensitization, the SMGs of the sensitized animals were recovered and processed for histologic examination. Samples of the SMG fractions used for sensitization were also examined by electron microscopy. The 25,000g and 100,000g fractions consistently induced extensive mononuclear cell infiltrates and exocrine gland destruction in the SMGs while the 10,000g and 40,000g fractions caused infrequent and minimal inflammatory cell infiltrates in the glands. These data, combined with the electron microscopic analysis of the fractions, suggest that the target antigens in EAS reside on particulate fractions from the SMG that have the characteristics of the cell surface (25,000g) and microsomes (100,000g).

Animals↗
PubMed1991

Experimental autoallergic sialadenitis in the LEW rat. III. Role of CD4+ T cells in EAS induction.

Experimental autoallergic sialadenitis (EAS) in the LEW rat is an induced autoimmune disease of the salivary tissues. EAS is characterized by a lymphocytic infiltration that consists of both CD4+ (helper/inducer T-cell subset) and CD8+ (cytotoxic/suppressor T-cell subset) T cells and results in the immune-mediated destruction of the exocrine salivary glands. To investigate the role that each of the T-cell subsets may have in the pathogenesis of EAS, LEW rats sensitized with WF SMG homogenate were injected with monoclonal antibodies to deplete or inactivate, in vivo, the CD4, CD5 (OX19; pan T lymphocyte), CD8, or RT6 (70% of peripheral T cells) T-cell populations. Treatment with the OX8 (CD8), OX19 (CD5), or W3/25 (CD4) only partially reduced in vivo the respective splenic or lymph node T-cell subsets when analyzed on Day 14, while treatment with DS4.23 (anti-RT6) resulted in greater than 95% depletion of RT6+ spleen and lymph node T cells. EAS incidence and severity was significantly reduced in the W3/25 (CD4) treatment group (11% incidence rate; histologic score 1.0) as compared to medium-injected controls (88% incidence rate; histologic score 2.9). Although the incidence and severity of EAS in the OX19 (71%; histologic score 1.7), OX8 (55%; histologic score 1.7), and RT6 (67%; histologic score 1.6) treatment groups appeared decreased, the reduction was not statistically significant. These results provide evidence that CD4+ T cells have an important role in EAS induction and demonstrate that in vivo treatment with anti-CD4 can ameliorate and/or prevent EAS in the LEW rat.

Animals↗
PubMed1991

Xylose-linked proteoglycan synthesis does not have a primary role in the control of secretory cell differentiation in salivary glands.

Xylose-linked proteoglycans, particularly chondroitin sulfate proteoglycan, have been shown to play a significant role in the regulation of salivary gland morphogenesis. The purpose of this study was to determine if xylose-linked proteoglycans are involved in the regulation of differentiation of salivary gland secretory cells. Embryonic rat submandibular salivary gland rudiments were cultured for 120 hr in the presence or absence of 0.75 to 1.0 mM p-nitrophenyl-beta-D-xylopyranoside (beta-D-xyloside), an inhibitor of xylose-linked proteoglycan assembly. beta-D-Xyloside has been shown to block submandibular gland morphogenesis (Thompson and Spooner, 1982). In the present study glandular morphogenesis was blocked in 93.3% of the rudiments cultured in the presence of beta-D-xyloside. However, secretory cell differentiation was observed in 71.4% of those rudiments in which morphogenesis had been inhibited. Biochemical evaluation confirmed that xylose-linked proteoglycan assembly had been inhibited by xyloside. These results indicate that while xylose-linked proteoglycans play a significant role in the control of salivary gland morphogenesis these molecules are not primary regulators for secretory cell differentiation within developing salivary glands.

Animals↗
PubMed1991

Epithelial-mesenchymal interactions in the development of salivary glands.

The full expression of both morphogenesis and secretory cell differentiation in salivary glands is modulated or controlled, at least in part, by interactions between the salivary epithelium and the surrounding mesenchyme. Salivary gland morphogenesis and cytodifferentiation are partially linked but independently regulated processes. This presentation reviews the information that establishes the role of various extracellular matrix molecules and direct epithelial-mesenchymal interactions in the induction, control, and maintenance of morphogenesis and secretory cell differentiation in salivary glands.

Animals↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗