PubMed Health⌕ Search

Biomedical subjects

L H Tang

Publications and source records attributed to L H Tang.

At least 37 records · Page 2Linked to original sources
PubMed1998

Telenzepine-sensitive muscarinic receptors on rat pancreatic acinar cells.

To identify the muscarinic subtype present on the rat pancreatic acinar cell, we examined the effects of different muscarinic receptor antagonists on amylase secretion and proteolytic zymogen processing in isolated rat pancreatic acini. Maximal zymogen processing required a concentration of carbachol 10- to 100-fold greater (10(-3) M) than that required for maximal amylase secretion (10(-5) M). Although both secretion and conversion were inhibited by the M3 antagonist 4-diphenylacetoxy-N-methyl-piperidine (4-DAMP) (50% inhibition approximately 6 x 10(-7) M and 1 x 10(-8) M, respectively), the most potent inhibitor was the M1 antagonist telenzepine (50% inhibition approximately 5 x 10(-10) M and 1 x 10(-11) M, respectively). Pirenzepine, another M1 antagonist, and the M2 antagonist methoctramine did not reduce amylase secretion or zymogen processing in concentrations up to 1 x 10(-5) M. Analysis of acinar cell muscarinic receptor by PCR revealed expression of both m1 and m3 subtypes. The pancreatic acinar cell has a distinct pattern of muscarinic antagonist sensitivity (telenzepine >> 4-DAMP > pirenzepine) with respect to both amylase secretion and zymogen conversion.

Animals↗
PubMed1998

A polyamine pathway-mediated mitogenic mechanism in enterochromaffin-like cells of Mastomys.

We have previously demonstrated that in Mastomys species proliferation of gastric enterochromaffin-like (ECL) cells is predominantly regulated by gastrin and by transforming growth factor-alpha (TGF-alpha) in the naive and neoplastic state, respectively. In this study we examined whether these intracellular mitogenic responses are mediated by polyamines and ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine biosynthesis. An ECL cell preparation of high purity was used to measure the effect of the polyamine derivatives putrescine, spermidine, and spermine on DNA synthesis by bromodeoxyuridine uptake. Both putrescine and spermidine augmented gastrin-stimulated, but not basal, DNA synthesis in naive cells. This proliferative response correlated with an increase in ODC activity that was partially inhibited (20%) by difluoromethylornithine (DFMO), an inhibitor of ODC (IC50, 30 pM). In contrast, all polyamines increased both basal and TGF-alpha-stimulated DNA synthesis as well as ODC activity in tumor ECL cells. DFMO completely inhibited the proliferative response of TGF-alpha (IC50, 3 pM). Thus polyamine biosynthesis is involved in proliferation of ECL cells and in particular the mitogenesis of tumor cells, suggesting a role for this pathway in the regulation of ECL cell transformation.

Animals↗
PubMed1998

Gastrin and the enterochromaffin-like cell: an acid update.

Gastrin is synthesized and secreted mostly in a heptadecapeptide form from neurocrine G cells located in the antrum. The biologically active sequence of the molecule is a C-terminal pentapeptide, which has been conserved across many species. Transcriptional regulation of gastrin mRNA synthesis is positively regulated by transforming growth factor-alpha (TGF-alpha) and inhibited by somatostatin (SST). The inactive precursor form is converted to the active molecule by several post-translation processing steps which include cleavage, C-terminal amidation, glycosylation, phosphorylation and sulfation. Aberrations in processing steps generate incompletely processed forms, particularly glycosylated progastrin, which may act as autocrine growth factors for gastrointestinal neoplasms. Gastrin release is stimulated by luminal aromatic amino acids and inhibited by a decrease in luminal pH. Other gastrin agonists include beta-adrenergic agents, acetylcholine, gastrin-releasing peptide (bombesin), TGF-alpha, and possibly the gastric pathogen, Helicobacter pylori. The principal peptide inhibitor of gastrin release is SST. The major physiological roles of gastrin include stimulation of acid secretion, regulation of mucosal cell lineage and mucosal cell proliferation. The fundic enterochromaffin-like (ECL) cell is the principal cellular transducer of the gastrin-acid signal. Activation of its gastrin/CCKB receptor results in histamine synthesis and release with consequent activation of the fundic parietal cell H2 receptor. An increase in luminal pH caused by acid inhibitory pharmacotherapy agents (particularly proton pump inhibitors) results in hypergastrinemia and ECL cell hyperplasia. Gastric carcinoids however appear occur in patients with multiple endocrine neoplasia type I syndrome, suggesting that an associated genomic defect is necessary. Gastrin is thus both a potent gastrointestinal trophic and histamine secretory agent. As a hormone it is a paradigm in the elucidation of both cellular secretory and growth factor induced cell proliferation.

Enterochromaffin-like Cells↗
PubMed1997

Gastrin receptor expression and function during rapid transformation of the enterochromaffin-like cells in an African rodent.

The enterochromaffin-like cell (ECL) cells of the stomach are principally regulated by gastrin via a gastrin/CCK(B) receptor (G[R]) which modulates both histamine secretion and cell proliferation. In the African rodent (mastomys) hypergastrinemia generated by the histamine-2 receptor antagonist (loxtidine) results in ECL cell hyperplasia and neoplasia at 8 and 16 weeks respectively. The expression, structure and function of the G(R) during transformation is however unknown. We utilized a pure (approximately 90%) preparation of ECL cells to evaluate alterations in the G(R) utilizing immunocytochemistry, Western blot analysis, reverse transcription polymerase chain reaction (RT-PCR), 5-bromo-2-deoxyuridine uptake and phosphorylation site analysis. Although the expression of ECL cell G(R) was upregulated at both mRNA (PT-PCR) and protein (Western analysis) level, its affinity to gastrin was decreased in the hyperplastic phase and lost during transformation. The coding sequence of the G(R) of mastomys tumor ECL cells was identical to that of normal ECL cells, parietal cells and the brain. However, the mRNA sequence of the third introcytoplasmic loop of the G(R) was significantly different to other species. In addition, the G(R) exhibited phosphorylation site on serine residue(s). We have thus noted a direct correlation between hypergastrinemia and G(R) alteration and function during ECL cell transformation. It is possible that the unique mastomys gastrin receptor mediated ECL cell transformation involves the novel phosphorylation sites and a divergence in the introcytoplasmic domain.

Animals↗
PubMed1997

The pivotal role of John S. Edkins in the discovery of gastrin.

John Sydney Edkins was born in London in 1863. After gaining two open scholarships, he attended Caius College, Cambridge and studied physiology under the tutelage of J.N. Langley and M. Foster. During this period he published on the chemical nature of pepsinogen with Langley. After qualifying as a medical doctor, he worked in Manchester before returning to London, where he succeeded E. Klein as Head of Physiology at St. Bartholomew's. For financial reasons he also worked part time at Bedford College for Women. In 1902 Bayliss and Starling overturned Pavlov's doctrine of the nervous regulation of gastrointestinal function by discovering the pancreatic secretagogue secretin-the first identifiable chemical messenger. Edkins applied a similar rationale to the stomach and in a classic series of experiments noted that injection of a pyloric mucous membrane extract resulted in gastric acid and pepsin secretion in anesthetized cats. In 1905 he named this putative active agent "gastrin." Although his ideas were initially accepted, the discovery of histamine in 1910 and the identification that extracts from other tissues had a similar physiologic effect raised serious questions regarding the validity of the existence of gastrin. Somewhat discouraged, Edkins pursued the teaching and training of women physiologists at Bedford College, where he later became Chairman of Physiology. Outside of science he successfully pursued other interests and became President of the British Croquet Association. The demonstration that gastrin was a unique antral stimulant of acid secretion by Komarov in 1938 was followed by the purification and elucidation of its chemical structure by Gregory and Tracy in 1964. Their work allowed final validation of Edkins' original hypothesis. Edkins died in London in 1940, not only fated to predecease the vindication of his hypothesis but unable to witness the evolution of his discovery into a paradigm for the hormonal regulation of secretory and proliferative cellular activity.

Animals↗
PubMed1997

Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today).

Because SRS identifies 90% of hepatic metastatic disease and the addition of other studies (ultrasonography, C.T. MRI, and selective mesenteric angiography) identities only 4% more, the identification of a primary lesion with SRS obviates for the most part the use of further investigations. If SRS is negative, additional studies should only be undertaken if surgery is contemplated. Because SRS may only localize 60%-70% of primary gut NETs, an additional 10%-15% may be identified by undertaking additional studies. The most sensitive test, STIR-MRI, should be undertaken next, but because it is not widely available, pancreatic protocol CT scan is almost as effective in identification of a primary lesion. If a primary gastrinoma cannot be identified by SRS or STIR-MRI, endoscopic ultrasonography should be undertaken because duodenal gastrinomas are often minute and multicentric. A similar strategy applies for insulinomas because up to 40% cannot be located by SRS and the majority are located in the pancreatic head. Thus, STIR-MRI followed by endoscopic ultrasonography is the most appropriate course. Although calcium provocation-angiography is highly effective in the identification of insulinomas, it is significantly more invasive and should be used only as a last resort. Of particular interest is the observation that in the study of gastrinomas, SRS altered clinical management in almost 50% of patients. This reflected the ability of SRS not only to identify the primary tumor location but clarify equivocal localization results generated by conventional imaging studies. It thus seems that the simplicity, superior sensitivity, high specificity, and cost-effectiveness of SRS mandate that it be the imaging modality in patients with gastrinomas. Because the cost of an SRS is $1800 and may obviate the need for multiple other topographic studies that are at least as expensive, the fiscal dictates further warrant the use of this study as the initial topographic investigation. These observations are probably applicable to all gut NETs, although the likelihood of primary identification in the instance of insulinoma patients may be somewhat less. The timely and cost-effective establishment of the type of NET, its primary site, and the detection metastatic spread will enable determination of the appropriate management strategy.

Algorithms↗
PubMed1997

Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells.

BACKGROUND & AIMS: Helicobacter pylori alterations in gastric acid output and mucosal proliferation may involve the enterochromaffin-like (ECL) cell. To test whether H. pylori affects ECL cell histamine secretion and proliferation, the effect of lipopolysaccharide (LPS) on ECL cell function in vitro was investigated. METHODS: Using a rat ECL cell preparation of high purity (+/-95%), basal and stimulated histamine secretion and DNA synthesis were measured by enzyme immunoassay and bromodeoxyuridine (BrdU) uptake, respectively. RESULTS: Escherichia coli LPS (10(-12) to 10(-6) mol/L) had no effect on basal and stimulated histamine secretion at concentrations of > 10(-6) mol/L. H. pylori LPS stimulated basal and gastrin-stimulated histamine secretion. These effects were completely inhibited by somatostatin (10(-10) mol/L) but not by the gastrin receptor antagonist L365,260 at 10(-6) mol/L. E. coli LPS had a weak stimulatory effect on ECL cell BrdU uptake at 10(-6) mol/L but had no effect on gastrin-stimulated BrdU uptake. H. pylori LPS did not stimulate basal synthesis but significantly increased (1.5-fold) gastrin-stimulated BrdU uptake. CONCLUSIONS: H. pylori influences both ECL cell proliferation and secretion in vitro. An interaction between H. pylori LPS and ECL cells may contribute to the reported abnormalities in acid secretion and gastric pathobiology noted in H. pylori infections.

Animals↗
PubMed1997

A 40-year analysis of 265 gastric carcinoids.

OBJECTIVES: Gastric carcinoid tumors were previously regarded as rare, benign neoplasms. Few data are available on the epidemiology of this lesion. METHODS: We have analyzed the End Results Group (1950-1969), the Third National Cancer Survey (1969-1971) and the Surveillance, Epidemiology, and End Results (SEER, 1973-1991) databases of the National Cancer Institute. The three files consist of 8305 carcinoid cases collectively, including 265 gastric carcinoids. RESULTS: The percentage of gastric carcinoids among all gastric malignancies has increased from 0.3% to 0.54%. The black:white ratio declined from 0.36 to 0.17 as well as the male:female ratio from 0.9 to 0.57. The age-adjusted incidence rates have increased in white females but are much higher for the black population. Gastric carcinoids are associated with other malignant neoplasms in 7.8% of cases. The 5-yr survival rates for localized lesions, with regional and with distant metastases, were 48.6%, 39.9%, and 10%, respectively. CONCLUSIONS: Gastric carcinoids have increased in incidence over the last 20 yr. This may represent either improved diagnostic techniques, increased awareness, or a real change in incidence. Poor 5-yr survival rates indicate that gastric carcinoid tumors exhibit an aggressive biological behavior.

Age Distribution↗
PubMed1997

Study of simplified measures for malaria surveillance in the late consolidation phase in China.

This paper presents the results of a study on simplified surveillance methods conducted in 23 pilot counties in 11 provinces and municipalities in China where reside 15 million people and malaria control has been in the late consolidation phase. Two simplified surveillance Schemes (A and B) taking treatment of clinical cases as the main measure were implemented in 1992-1994. The rate of annual blood examination for case detection was 1.0% in pilot Scheme A, while in areas of scheme B it was 0.3%. The implementation of both Scheme A and Scheme B, simplified or without treatment of infection foci and management of mobile populations, acquired satisfactory effects against malaria. Consequently, malaria incidence was declining steadily, only a few indigenous and introduced cases were detected. The parasite rate in residents and the IFA positive rate in children were very low. The results of pilot studies and cost-effectiveness analysis indicated that Scheme B is effective, rational and economic, and can be implemented to replace the routine surveillance measures in areas where malaria has been at the late consolidation phase in China.

Adult↗
PubMed1997

Genetic differentiation among three populations of Anopheles minimus of Guangxi and Yunnan Provinces in the People's Republic of China.

Electrophoretic studies were carried out on isozymes of 3 populations of Anopheles minimus collected from Guangxi and Yunnan Provinces of the People's Republic of China in 1993. Eight proteins were analyzed by 5% polyacrylamide gel electrophoresis. The most variable population, 'Yunnan-Field' (Y-F), was highly polymorphic at 14 of 20 loci (P = 0.700) with an average heterozygosity H of 0.340. P values of 0.500 and 0.700, and H values of 0.220 and 0.210 were obtained for each from 'Guangxi-Lab' (GX-L) and 'Yunnan-Lab' (Y-L), respectively, Nei's genetic distances (D) between Y-L and GX-L, Y-F and GX-L, and Y-F and Y-L were 0.1131, 0.1946 and 0.1069, respectively. These results suggest that GX-L is distant from the 2 other populations, Y-L and Y-F, and that this genetic differentiation between the 2 populations of Yunnan and Guangxi Provinces corresponds to the forms A and B, which were morphologically classified by Xu et al (unpublished).

Animals↗
PubMed1996

Effect of link protein concentration on articular cartilage proteoglycan aggregation.

Previous work has shown that alterations in proteoglycan aggregates are among the first changes detected with aging, disuse, and degeneration of articular cartilage, yet the cause or causes of these alterations remain unknown. To determine if differences in link protein concentration can explain alterations in the assembly, size, and stability of articular cartilage proteoglycan aggregates, we isolated proteoglycan monomer (aggrecan) and link protein from adult bovine articular cartilage and then assembled proteoglycan aggregates from aggrecan and 0.8% hyaluronan relative to aggrecan weight, in the presence of 0, 2, 4, 6, 8, 10, 15, and 20% concentrations of link protein relative to aggrecan weight. We determined the amount, sedimentation coefficient, and stability of the aggregates by analytical ultracentrifugation and measured their dimensions by electron microscopy with use of the monolayer technique. Increased aggregate size, as determined by ultracentrifugation, was directly correlated with an increased number of aggrecans per aggregate and with increased hyaluronan length, as determined by electron microscopy. The concentration of link protein significantly influenced aggregation: concentrations of 6-8% produced maximum aggregation, aggregate stability, and uniformity of aggrecan spacing; concentrations greater than 10% led to the formation of superaggregates (aggregates with sedimentation velocities greater than 100 S that may result from linking two or more hyaluronan filaments) but decreased aggregate stability; and concentrations of less than 4% link protein significantly decreased aggregation, the size and stability of aggregates, and the regularity of aggrecan spacing. The latter observations suggest that a decline in the concentration of link protein could decrease the organization and stability of the articular cartilage matrix.

Aggrecans↗
PubMed1996

Somatostatin receptor regulation of gastric enterochromaffin-like cell transformation to gastric carcinoid.

BACKGROUND: Although somatostatin is recognized as an inhibitor of neuroendocrine cell secretion, its effect on cell proliferation has not been well defined. Generation of low acid and hypergastrinemia through irreversible H2-receptor blockade (loxtidine) in the African rodent mastomys results in gastric carcinoids (ECLomas) within 4 months. This study was undertaken to evaluate and characterize the precise somatostatin receptor (SSTR) subtype on the mastomys enterochromaffin-like (ECL) cell and to define its role in the regulation of ECL cell secretion and proliferation. METHODS: A pure preparation (approximately 90%) of ECL cells was derived by a combination of pronase digestion and density gradient separation. We assessed the effect of somatostatin (10(-15) to 10(-7) mol/L) on gastrin-stimulated ECL cell histamine secretion and DNA synthesis (bromodeoxyuridine uptake). SSTR2 subtype was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) using gene specific primers and mRNA isolated from normal and hypergastrinemia-induced ECLoma. The polymerase chain reaction product was confirmed by Southern analysis, subcloned, and sequenced. RESULTS: Somatostatin inhibited both gastrin-stimulated histamine secretion (IC50, 5 x 10(-13) mol/L) and DNA synthesis (IC50, 10(-10) mol/L). SSTR2 was identified in the mastomys' brain, and both normal and tumor ECL cells and comparison of the brain and ECL cell SSTR2 nucleotide sequences revealed homology of 99%. CONCLUSIONS: The SSTR2 is expressed by the mastomys' ECL cell and ECLoma. Receptor activation inhibits both ECL cell secretory and proliferative functions.

Animals↗
PubMed1996

Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.

Mastocytosis is characterized by accumulations of mast cells in various organs (1). Most cases are indolent and confined to the skin, where discrete mast cell infiltrates are associated increased epidermal melanin, a clinical picture known as urticaria pigmentosa (UP). Other forms of mastocytosis combine UP with aggressive involvement of other organs or with haemotologic abnormalities (1-4). It is not known whether all forms of mastocytosis are true neoplasms or whether some might represent reactive hyperplasias (5-7). The c-KIT proto-oncogene encodes a type III receptor tyrosine kinase (KIT) that is critical to the development and survival of mast cells and melanocytes (8-11). The ligand for KIT (KL) can stimulate mast cell development, proliferation, and mediator release (9,12-17), as well as melanocyte proliferation and pigment production (18-20). To determine the role of c-KIT in the pathogenesis of mastocytosis, we examined tissue and cells isolated from a patient with UP and aggressive systemic mastocytosis with massive splenic involvement. We found a mutation that results in constitutive activation and expression of c-KIT in mast cells of both skin and spleen. This is the first in situ demonstration of an activation c-KIT mutation in neoplastic cells. It also demonstrates the clonal and neoplastic nature of this form of mastocytes.

Adult↗
PubMed1996

rab3D protein is a specific marker for zymogen granules in gastric chief cells of rats and rabbits.

BACKGROUND & AIMS: Pepsinogen secretion from gastric chief cells requires a series of intracellular vesicle interactions. The final step of exocytosis involves fusion of secretory granules with the plasmalemma, culminating in the release of the digestive enzyme pepsinogen into the lumina of gastric glands. A group of specialized proteins tht confer membrane recognition, targeting, and fusion events are involved in regulated exocytosis. The aim of this study was to examine the distribution of rab3D, a low-molecular-weight guanosine 5'-triphosphate-binding protein, in gastric chief cells. METHODS: rab3D immunoreactivity was evaluated by Western blot analysis and by immunocytochemical studies at both confocal and electron-microscopic levels. RESULTS: rab3D immunoreactivity was specifically localized to the secretory granules in chief cells. Double labeling of gastric glands with rab3D and pepsinogen antibodies confirmed rab3D immunoreactivity localization to chief cells but not acid-secreting parietal cells. Immunoelectron microscopy revealed a near exclusive localization of the rab3D-like protein to the cytoplasmic face of the zymogen granules. After short-term stimulation consequent to feeding, rab3D immunoreactivity appeared to relocate from an apical region of duct cells to an unidentified cytoplasmic compartment. CONCLUSIONS: The localization and redistribution of the rab3D-like protein in the chief cell suggests that it may play an important role in regulated exocytosis.

Animals↗
PubMed1996

Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion.

BACKGROUND & AIMS: Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, serotonin, gamma-amino-butyric acid, neurokinins A and B, neurotensin, neuropeptide Y, peptide YY, gastrin-releasing peptide, somatostatin, and [Met5]enkephalin. Although some of these agents have been implicated as regulators of gastric acid secretion, their site and mechanism of action is not well understood. The aim of this study was to investigate whether local gastric neurotransmitters modulate acid secretion by regulating basal and gastrin-driven enterochromaffin-like (ECL) cell histamine release. METHODS: The effects of the above agents were investigated in a short-term 90%-95% pure ECL cell culture system. Cells were incubated with either the neuromodulator alone or in combination with gastrin for 10-40 minutes, and histamine secretion was measured by enzyme immunoassay. RESULTS: Acetylcholine, isoproterenol, and vasoactive intestinal polypeptide significantly stimulated basal and gastrin-driven histamine secretion, whereas calcitonin gene-related peptide and somatostatin inhibited basal and gastrin-driven histamine secretion. The M1 muscarinic receptor antagonist pirenzepine dose dependently inhibited the action of acetylcholine, whereas the M3 receptor antagonist 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride had no effect. the rest of the evaluated agents had no effect on ECL cell histamine secretion. CONCLUSIONS: These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.

Acetylcholine↗