Biomedical subjects

A H Mulder

Publications and source records attributed to A H Mulder.

222 records · Page 13Linked to original sources

PubMedDate not supplied

Peripheral injection of DNS-RFa, a FMRFa agonist, suppresses morphine-induced analgesia in rats.

The present results demonstrate an antagonistic effect of DNS-RFa on morphine-induced analgesia in rats. This confirms previous evidence presented by others on the effects of FMRFa-related peptides when applied centrally. Unlike these peptides, however, it is shown here that DNS-RFa is effective upon peripheral injection. The effects of DNS-RFa on morphine-induced analgesia were dose-dependent (ED50 = 0.5 mg/kg). DNS-RFa alone (5 mg/kg) did not affect the control level of nociception. Peripheral injection of FMRFa (5 mg/kg) did not affect morphine-induced analgesia. DNS-RFa defines the minimal configuration to activate neuronal FMRFa receptors in the pond snail. The present report suggests also that in vertebrates the Arg-Phe-NH2 sequence is essential and that DNS-RFa readily penetrates the blood-brain barrier.

Analgesia↗

PubMedDate not supplied

Kappa- and delta-opioid receptor agonists differentially inhibit striatal dopamine and acetylcholine release.

At least three different families of endogenous opioid peptides, the enkephalins, endorphins and dynorphins, are present in the mammalian central nervous system (CNS). Immunocytochemical studies have demonstrated their localization in neurones, which supports the view that these peptides may have a role as neurotransmitter or neuromodulators. However, the target cells and cellular processes acted upon by the opioid peptides are still largely unknown. One possible function of neuropeptides, including the opioid peptides, may be presynaptic modulation of neurotransmission in certain neuronal pathways, for example, by inhibition or promotion of neurotransmitter release from the nerve terminals. Here we report that dynorphin and some benzomorphans potently and selectively inhibit the release of (radiolabelled) dopamine from slices of rat corpus striatum, by activating kappa-opioid receptors. In contrast, [Leu5]enkephalin and [D-Ala2, D-Leu5]enkephalin selectively inhibit acetylcholine release by activating delta-opioid receptors.

Acetylcholine↗

PubMedDate not supplied

Distribution of dopamine-immunoreactive cell bodies in the guinea-pig brain.

The distribution of dopamine (DA)-containing neurons in the guinea-pig brain was investigated immunohistochemically using antibodies raised against glutaraldehyde-conjugated DA. Light microscopical studies revealed the presence of nearly 50,000 DA-immunoreactive cells, localized throughout the hypothalamus and the midbrain. With a few exceptions the dopaminergic cell groups identified by different (immuno)histochemical techniques in the rat were also demonstrated in the guinea-pig brain. These include tyrosine hydroxylase-immunoreactive positive, dopamine-beta-hydroxylase-immunoreactive negative cells in the medial hypothalamus, the ventral tegmental area, the substantia nigra and the dorsal raphe nucleus. A group of dopaminergic cell bodies, not present in the rat, was found to extend from the nucleus retrochiasmaticus into the rostral part of the eminentia mediana. Also at variance with the rat, the guinea-pig lacked DA-immunoreactive cells in a number of homologous areas corresponding to the A15- and A8 cell groups and partly, the A14- and A10 cell groups. However, in general, the localization of dopaminergic cell bodies in the guinea-pig brain appeared similar to that in the rat brain.

Animals↗

PubMedDate not supplied

The localization of histidine decarboxylase-immunoreactive cell bodies in the guinea-pig brain.

In this immunocytochemical study the localization of histaminergic neurons in the guinea-pig brain was investigated using an antiserum raised against rat histidine decarboxylase. The total number of histaminergic cells appeared to be between 4200 and 4800, which is considerably higher than the number reported by others for the rat brain. The major groups of histaminergic cells were confined to the nucleus mammillaris medialis and the nucleus caudalis magnocellularis (CM). Three minor groups of histaminergic cells were found, respectively, in the area of the nucleus premammillaris ventralis, along the ventral aspect of the nucleus supramammillaris and in the nucleus caudalis magnocellularis postmammallaris (PCM). Finally, some scattered histaminergic cell bodies were observed in the nucleus mammillaris posterior. The most ventrally situated groups of histaminergic cells, i.e. the CM and PCM groups, extend into a medial direction as a string of cell bodies which is possibly located in the pia and likely bridges these bilaterally situated cell groups. Some of the histaminergic cell groups found in the guinea-pig brain appear to be absent or much smaller in the rat brain. These data indicate that the histaminergic neuronal systems in the guinea-pig and the rat brain are quite similar with regard to their overall organization, but also appear to display some differences, both with regard to the number and, at least partly, the localization of the cell bodies.

Animals↗

PubMedDate not supplied

Intragraft monitoring of rejection after prophylactic treatment with monoclonal anti-interleukin-2 receptor antibody (BT563) in heart transplant recipients.

BACKGROUND: Anti-interleukin-2 receptor monoclonal antibodies have been used successfully in the prevention of rejection in cardiac allografts in several animal models. METHODS: In an open randomized study murine monoclonal CD3 antibody and BT563, a murine anti-interleukin-2 receptor monoclonal antibody, were given as rejection prophylaxis during the first week after heart transplantation. Cyclosporine therapy was initiated at the third postoperative day. RESULTS: In half the BT563-treated patients an early rejection was histologically shown at week 1, whereas heart transplant recipients treated with murine monoclonal CD3 antibody had a rejection incidence at week 1 of only 9%. During BT563 treatment CD25-positive cells (i.e., cells bearing the interleukin-2 receptor) were not detectable in peripheral blood. However, immunohistologic studies of endomyocardial biopsy specimens taken 1 week after transplantation showed the presence of CD25-positive cells within these specimens in 8 of 10 (80%) of patients with rejection. In patients without rejection CD25-positive cells were present in the biopsy specimens of only two of nine patients (22%). Reverse-transcriptase polymerase chain reaction studies on biopsy material showed the presence of messenger RNA for the interleukin-2 receptor in all and for interleukin-2 in three of five (60%) of biopsy specimens of rejecting grafts. CONCLUSIONS: Although CD25-positive cells were not detectable in peripheral blood during BT563 treatment, these cells were at the same time found to be present within 80% of the endomyocardial biopsy specimens from the rejecting grafts. By initiating cyclosporine treatment at day 0, the synergistic effect of combining cyclosporine and anti-interleukin-2 receptor monoclonal antibodies may result in a lower rejection incidence.

Animals↗

PubMedDate not supplied

DNA ploidy as a prognostic factor for patients with an adenocarcinoma in Barrett's esophagus.

BACKGROUND/AIMS: The role of DNA ploidy of tumor cells as a prognostic factor for survival after resection was evaluated in 40 patients with an adenocarcinoma in Barrett's esophagus (28 men and 12 women; mean age, 61 years). MATERIALS AND METHODS: After resection of the esophagus, staging was performed according to the TNM-classification (UICC 1987). Tumor tissue specimens were reviewed for the histological differentiation grade and flow cytometry was performed on paraffin embedded tissue according to the method described by Hedley. RESULTS: There was no significant correlation between DNA-ploidy and TNM-stage or histological differentiation grade of the tumor. DNA ploidy, stage and grade as prognostic factors for the survival were evaluated by multivariate analysis. DNA ploidy significantly (p= 0.04) correlated with survival, also univariately. Patients with diploid tumors had 3- and 5-year survival rates of 51% and 25% respectively, as compared to 10% and 0% respectively for patients with aneuploid or tetraploid/increased G2 tumors. CONCLUSION: DNA ploidy is an independent prognostic factor for the survival of patients with an adenocarcinoma in Barrett's esophagus.

Adenocarcinoma↗