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Biomedical subjects

R Hof

Publications and source records attributed to R Hof.

11 recordsLinked to original sources

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.

Adjuvants, Immunologic↗

Contribution of CD40-CD154-mediated costimulation to an alloresponse in vivo.

BACKGROUND: Costimulation through CD40-CD154 plays an important role in T-cell activation. Although systemic administration of anti-CD154 antibody prevents or delays rejection of organ allografts in animal models, the molecular mechanisms responsible for this effect are not well defined. METHODS: We have previously demonstrated that priming of mice (H2d) with CD40-/- but not with wildtype naive B cells (H2b) leads to alloantigen-specific T-cell hyporesponsiveness in vitro. In the present study, we investigated whether such priming modifies allograft rejection in a major histocompatibility complex-mismatched murine cardiac transplantation model. RESULTS: Priming of hosts with donor-specific CD40-/- B cells delayed rejection of subsequently transplanted wild-type cardiac allografts by 8.0 days (P<0.001). The lack of CD40 on the cardiac graft delayed rejection in unprimed or primed hosts by 3-5 days. Prolongation of graft survival correlated with the failure of infused CD40-/- B cells to express B7.2 and ICAM-1 in vivo. CONCLUSIONS: Our data suggest that CD40-CD154 costimulation contributes to T cell priming to alloantigens in vivo and to a second set rejection phase in which donor antigens are presented to primed T cells.

Animals↗

Effects of hCGRP I and II on gastric blood flow and acid secretion in anesthetized rabbits.

Effects of intravenously administered human calcitonin gene-related peptides (hCGRP) I and II on regional blood flow and gastric acid secretion were examined in barbiturate-anesthetized rabbits. Blood flow was measured by injection of radioactively labeled microspheres at 0, 10, 20, 30, and 60 min. hCGRP I and II and vehicle were infused intravenously in five rabbits in rising doses of 0.01 (0-10th min), 0.03 (11-20th min), and 0.1 microgram.kg-1.min-1 (21-30th min). hCGRP I and II increased gastric blood flow dose dependently. Moreover, hCGRP I raised regional conductance (inverse of vascular resistance) in the stomach, duodenum, heart, brain, and skeletal muscle. As a result of the increased total peripheral conductance the mean arterial pressure was reduced, but the cardiac output remained unchanged. hCGRP II increased blood flow and conductance selectively in the stomach and the pancreas. The total peripheral conductance and mean arterial pressure remained unchanged. Apparently, hCGRP II exerts a more localized effect on the stomach than hCGRP I. hCGRP I and II did not affect basal gastric acid secretion. Pentagastrin-stimulated acid secretion was increased by 28% with hCGRP I (0.025 micrograms.kg-1.min-1) and decreased by 27% with hCGRP II (0.025 micrograms.kg-1.min-1). The inverse effect of hCGRP I and II and the parallel stimulation of blood flow brought about with hCGRP I and II indicate a different mode of action of the peptides on gastric blood flow and gastric acid secretion.

Animals↗

[Eosinophilic gastroenteritis].

Eosinophilic gastroenteritis represents a very rare inflammatory disease of the stomach and bowel. Aetiologically an allergic diathesis must be assumed, but it is only very seldom that a particular allergen can be identified as being responsible for any case. Characterized by peripheral blood eosinophilia and eosinophilic infiltration of various parts of the gastro-intestinal tract, together with disturbed gastro-intestinal function, complications can arise in this disease requiring surgical intervention. In general, however, conservative therapy is adequate. The clinical features are discussed on the basis of an own case report.

Duodenum↗

An investigation of S-100 protein in embryonic dental papillae of rats.

We attempted to identify S-100 protein, a marker of neural crest tissue, within cells of the developing dental papillae of 18-day rat fetuses by means of the immunoperoxidase technique. Although there is experimental evidence that dental papillae are derived from neural crest, no marker protein was identified in this study.

Animals↗

Hemodynamic changes in hypernatremic dehydration in the mini-pig.

Hypernatremic dehydration with metabolic acidosis and azotemia was experimentally induced in the mini-pig by feeding a hypertonic NaCl and NH4Cl solution wit nasogastric tube. After a loss of 19% of initial body weight within 32 hours, the following hemodynamic changes were observed: the heart rate rose, the arterial blood pressure was maintained, but cardiac output fell to 80% of its initial value. There was a redistribution of this lowered cardiac output with unchanged blood flow to heart, brain, adrenals and skeletal muscle. The flow to these vital organs was diverted to selective vasoconstriction of spleen, pancreas, gastrointestinal tract and kidneys. Quantitatively the contribution from the latter two organs was the most important.

Animals↗

[The Göttinger minipig as a laboratory animal. 5. Communication: cardiac output, its regional distribution and organ blood flow (author's transl)].

In 16 juvenile minipigs weighing 3.08 kg an average cardiac output of 23 ml/100 g body weight was measured with the dye-dilution method. The microsphere technique was used to assess distribution of cardiac output and organ blood flow. In 12 adult minipigs with a mean body weight of 21.5 kg the cardiac output of 14 ml/100 g body weight was measured with an electromagnetic flowmeter. The values of total systemic and organic blood flow correlated well with those of man and partly with those of other laboratory animals.

Animals↗

Regional vascular responses to asphyxia in the rabbit.

Organ blood flow was measured in eight spontaneously breathing male New Zealand white rabbits exposed to a 50 min period of asphyxia. The results were compared with eight control animals. Cardiac output and arterial pressure did not change. There was increased flow to the heart, brain and diaphragm. Flow to the kidneys and adipose tissue was reduced. Flow to the gastro-intestinal tract, liver, skeletal muscle and carcass was unchanged. Prolonged moderate asphyxia produces preferential blood supply to vital organs and maintains flow to the skeletal musculature and the gastro-intestinal tract; their blood supply is diverted mainly from the kidneys. These changes are similar to those seen in haemorrhagic and endotoxic shock in the rabbit.

Animals↗