PubMed Health⌕ Search

Biomedical subjects

D Tendler

Publications and source records attributed to D Tendler.

10 recordsLinked to original sources
PubMed2002

Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers.

BACKGROUND AND AIMS: Escherichia coli heat labile enterotoxin (LT) at doses of 5 micro g or 10 micro g has adjuvant activity for oral immunisation in humans infected with Helicobacter pylori, but causes severe diarrhoea. This study was undertaken to establish a safe and effective dose of LT, to confirm the safety of recombinant urease, and to compare the immunogenicity of orally compared with enterically delivered urease. METHODS: 42 healthy adults without present or past H pylori infection were randomised to receive 60 mg recombinant H pylori urease in soluble or in encapsulated form, given with doses of LT ranging from 0 micro g to 2.5 micro g. Four oral doses were administered at day 1, 8, 29, and 57. Specific IgG, IgA, and antibody secreting cells were measured as well as total alpha4beta7 integrin positive lymphocyte responses. RESULTS: Enterically delivered urease was well tolerated and no serious adverse events occurred. Mild diarrhoea (one to four loose stools) occurred after the first immunisation in 50% (6 of 12) of the volunteers exposed to 2.5 micro g LT (p=0.06; paired t test, compared with baseline) but not in volunteers exposed to lower LT doses. Immune responses occurred in five (p=0.048; Fisher's exact test), one, two, and one of six subjects exposed to 2.5 micro g, 0.5 micro g, 0.1 micro g, and no LT, respectively. Significant CD4(+), CD69(+), and CD45RO(hi) responses occurred over time among alpha4beta7(hi) lymphocytes in volunteers receiving 2.5 micro g LT. Enterically delivered urease induced higher lymphocyte responses than soluble urease. CONCLUSIONS: The safety of H pylori urease is confirmed. Oral LT may conserve its adjuvant activity at low doses with minimal side effects.

Adjuvants, Immunologic↗
PubMed1997

Erythropoietin gene regulation depends on heme-dependent oxygen sensing and assembly of interacting transcription factors.

Studies on erythropoietin (Epo) gene expression have been useful in investigating the mechanism by which cells and tissues sense hypoxia. Both in vivo and in Hep3B cells. Epo production is induced not only by hypoxia but also by certain transition metal (cobalt and nickel) and by iron chelation. When Hep3B cells were incubated in an iron deficient medium, Epo mRNA expression was enhanced fourfold compared to Hep3B cells in iron enriched medium. Epo induction by cobalt was inversely related to iron concentration in the medium, indicating competition between the two metals. Under hyperbaric oxygen, cobalt induction of erythropoietin mRNA was modestly suppressed while nickel induction was markedly enhanced. These recent observations support the proposal that the oxygen sensor is a heme protein in which cobalt and nickel can substitute for iron in the porphyrin ring. The up-regulation of Epo gene transcription by hypoxia depends on at least two known DNA binding transcription factors, HIF-1 and HNF-4, which bind to cognate response elements in a critical approximately 50 bp 3' enhancer. Hypoxia induces HIF-1 binding. HNF-4, an orphan nuclear receptor constitutively expressed in kidney and liver, binds downstream of HIF-1 and cooperates with HIF-1, contributing importantly to high level and perhaps tissue specific expression. The C-terminal activation domain of HNF-4 binds to the beta subunit of HIF-1. The C-terminal portion of the alpha subunit of HIF-1 binds specifically to p300, a general transcriptional activator. Hypoxic induction of the endogenous Epo gene in Hep3B cells as well as an Epo-reporter gene was fully inhibited by E1A, an adenovirus protein that binds to and inactivates p300, but only slightly by a mutant E1A that fails to bind to p300. Moreover, overexpression of p300 enhanced hypoxic induction. Thus, it is likely that in hypoxic cells, p300 or a related family member plays a critical role in forming a macromolecular assembly with HIF-1 and HNF-4, enabling transduction from the Epo 3' enhancer to the apparatus on the promoter responsible for the initiation of transcription.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1992

Hypoxia increases extracellular concentrations of excitatory and inhibitory neurotransmitters in subsequently induced seizure: in vivo microdialysis study in the rabbit.

It is uncertain whether a brief hypoxic exposure exerts long lasting effects on central nervous system amino acid neurotransmission. The purpose of this study was to test the hypothesis that a short period of hypoxia would affect release of excitatory and inhibitory amino acids during subsequent bicuculline-induced seizure. Utilizing in vivo microdialysis in cerebral cortex of rabbits, we observed no significant increase in extracellular fluid (ECF) concentrations of the excitatory amino acids, glutamate and aspartate, or the inhibitory amino acids, GABA and taurine, during a 30-min exposure to hypoxia (FiO2 = 0.08). In addition, there was no significant change in these amino acids during uncomplicated seizure. However, when seizure was complicated by a preceding period of hypoxia, there was a marked and progressive rise in both excitatory and inhibitory amino acids in ECF. We conclude that a short period of hypoxia, which itself does not cause changes in ECF concentrations of excitatory amino acids, may nonetheless contribute to neuronal injury by altering the levels of ECF amino acids during a subsequent insult.

Animals↗
PubMed1988

Cholecystokinin (CCK)-33 stimulates insulin secretion from the perfused rat pancreas: studies on the structure-activity relationship.

Cholecystokinin (CCK)-33 is known to stimulate insulin secretion. Presently, using the perfused rat pancreas, we have characterized the active site in the CCK-33 molecule that is responsible for this effect by the use of different CCK fragments. We found that CCK-33, CCK-8 and CCK-7 (1 nM) all significantly stimulated insulin secretion in the presence of 4.4 mM or 6.7 mM glucose. However, CCK-7 was much less potent than the longer forms. In contrast, CCK-4, CCK-6 and CCK-33 (1-21) had no effect on insulin secretion. We conclude that the shortest CCK-form that stimulates insulin secretion at 1 nM is the C-terminal heptapeptide CCK-7. However, CCK-8 is much more potent than CCK-7 in this respect.

Animals↗
PubMed1988

Cholecystokinin-33 potentiates and vasoactive intestinal polypeptide inhibits gastric inhibitory polypeptide--induced insulin secretion in the perfused rat pancreas.

Gastric inhibitory polypeptide (GIP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) stimulate insulin secretion. In this study we investigated whether CCK-33 and VIP could influence the insulinogenic effect of simultaneously administered GIP and 6.7 mmol/l glucose in the perfused rat pancreas. We found that at 0.1 nmol/l, GIP markedly potentiated glucose-induced insulin release whereas CCK-33 and VIP had a weak stimulatory effect and only during the late phase. At this low dose level, CCK-33 potentiated but VIP inhibited the late phase of insulin release stimulated by glucose and GIP. At 1.0 nmol/l, GIP, CCK-33, and VIP markedly potentiated both phases of glucose-induced insulin secretion. At this dose level CCK-33 and GIP exerted additive stimulatory effects on the late phase of insulin release triggered by glucose. In contrast, 1.0 nmol/l VIP inhibited insulin secretion augmented by glucose and GIP. In summary 1) GIP, CCK-33 and VIP all potentiate glucose-induced insulin secretion from the perfused rat pancreas, and 2) CCK-33 potentiates and VIP inhibits GIP-induced insulin secretion. We suggest that interactions of this kind are of importance for the precise regulation of insulin secretion.

Animals↗
PubMed1986

Potentiation of glucose-induced insulin secretion in the perfused rat pancreas by porcine GIP (gastric inhibitory polypeptide), bovine GIP, and bovine GIP(1-39).

Porcine GIP (gastric inhibitory polypeptide) potentiates glucose-induced insulin secretion under a variety of experimental conditions. Recently GIP was isolated also from bovine intestine, and found to differ from porcine GIP by having isoleucine instead of lysine in position 37. We have compared the effects of porcine GIP to that of bovine GIP and bovine GIP(1-39) on glucose-induced insulin secretion from the perfused rat pancreas. We found that porcine GIP, bovine GIP, and bovine GIP(1-39) all strongly potentiated both first and second phases of glucose-induced insulin secretion (glucose concentration 6.7 mM; polypeptide concentration 1 nM). There was no significant difference between the polypeptides with regard to the potency to potentiate glucose-induced insulin secretion. We conclude that bovine GIP, as porcine GIP, potentiates glucose-induced insulin secretion, and that the insulinotropic activity of GIP is not confined to the last three amino acids at the C-terminal end.

Animals↗
PubMed1983

Effects of PHI on hormonal secretion from perfused rat pancreas.

Effects of the novel gastrointestinal polypeptide PHI with N-terminal histidine, C-terminal isoleucine amide, and 27 amino acids have been studied in isolated perfused rat pancreas. PHI increased the release of insulin, glucagon, and somatostatin. The amounts of these hormones released were strictly dependent on the prevailing glucose concentrations. In the absence of glucose, PHI (1 nmol/liter) stimulated glucagon release. In the presence of 4.4 and 6.7 mmol/liter glucose, the same dose of this peptide stimulated insulin and somatostatin release. In the presence of 16.7 mmol/liter glucose, only insulin secretion was increased by PHI. When arginine was used as a secretagogue, PHI (10 nmol/liter) potentiated secretion of insulin, glucagon, and somatostatin. Thus, PHI may take part in the regulation of the function of the pancreatic A, B, and D cells.

Animals↗
PubMed1978

Training in prevention: an educational model for social work students.

Graduate schools of social work have made infrequent use of public health settings as a locus for practice education and a particular resource for learning in prevention. This report is on a project aimed at the development of an educational model in preventive work with families and children, using a student unit in fieldwork in a county health department. The 3-year project emphasizes early intervention with concern for developmental and life cycle tasks of families. Ongoing evaluation of process indicates clearer identification of populations "at risk" and changes in student appreciation of collaborative roles with other disciplines in patient care, as well as specific learning tasks and roles associated with screening, case finding, referral, and treatment.

Adolescent↗