Search PubMed⌕ Search

Biomedical subjects

C Nissen

Publications and source records attributed to C Nissen.

At least 163 records · Page 9Linked to original sources
PubMed1981

Permeability of blood-brain barrier to DSIP peptides.

An improved radioimmunoassay (RIA) for delta sleep-inducing peptide (DSIP) was used to study the permeability of the blood-brain barrier (BBB) to DSIP peptides. Although the synthetic analog [D-Ala3]-DSIP reacts fully in the assay, at least 8 of the 9 amino acids of the naturally occurring DSIP sequence are required for recognition by the antibody. A significant increase in DSIP-like immunoreactivity found in rat brain in one part of the study after peripheral injection of DSIP indicated, therefore, that some peptide crossed the BBB. The much higher levels found in brain tissue after intracarotid administration of [D-Ala3]-DSIP as compared with DSIP made it unlikely that non-specific leakage of peptide across the BBB was the only explanation. Furthermore, the findings after infusion with saline for one minute tended to rule out contamination of brain tissue by peptide remaining in blood. Thus, the results provide additional evidence that one of the ways peptides administered peripherally can influence the brain is by transport across the BBB essentially intact.

Animals↗
PubMed1981

DSIP-like immunoreactivity in the developing rat brain.

Delta sleep-inducing peptide (DSIP) is a naturally occurring nonapeptide that has been reported to affect sleep. The concentration of DSIP-like material was measured by a highly specific radioimmunoassay in brain tissue from developing rats. DSIP-like immunoreactivity was present in fetal brain at increased levels shortly before birth. In one experiment, a significant elevation in the concentration of the peptide occurred at postnatal day 20, but in a second, similar, study the increase occurred later. No marked differences in the levels of DSIP-like immunoreactivity were found in the brains of rats injected 2 months earlier with DSIP or among 10 parts of brains obtained at postnatal day 20. Regardless of the function of DSIP, it is available to the rat throughout early development.

Age Factors↗
PubMed1981

High T cell colony numbers do not reflect immune competence.

The number of T cell colonies growing from ficoll separated PHA-stimulated peripheral blood cells was compared to 3H-thymidine uptake in 133 normal donors of all ages. Unexpectedly, the two parameters did not correlate: The tendency of growing cells to aggregate during the incubation period resulted in few, but large spherical colonies in persons who by young age and high counts for thymidine uptake were judged to have good T cell function. This clustering effect was less pronounced in old persons and those with a low PHA response; it was virtually absent in 17 of 18 patients with undoubted cellular immune deficiency early after allogeneic bone marrow transplantation. This resulted in a growth pattern consisting of a high number of small scattered colonies. The capacity of growing cells to aggregate was sensitive to sublethal irradiation. We conclude that the number of T cell colonies growing from a given cell suspension not only depends on the number of lymphocytes responding to the mitogen. It is negatively determined by the drive of growing cells to cluster. This phenomenon deserves further study, since it appears to be a parameter of cellular immune competence which is not readily recognized with 3H thymidine incorporation.

Adolescent↗
PubMed1980

[Experience with intensive plasma exchange].

Experience with a total of 49 plasma exchanges in 14 patients is reported. All exchanges were performed with the Aminco cellseparator in an attempt to remove documented or suspected antibodies completely. Indications were ABO-barrier before bone marrow-transplantation (6), acute rejection following renal transplantation (3), autoimmune diseases (3), Moschowitz disease, antithrombocytic antibodies and hepatic coma (1 each). The technique was modified to make it possible routinely to exchange 121 of plasma in 4 hours with no major untoward side effects even in anuric or thrombopenic patients. Complete removal of circulating antibodies was possible and often followed by impressive clinical benefit.

ABO Blood-Group System↗
PubMed1980

Naloxone-like actions of MIF-1 do not require the presence of the pituitary.

The actions of peripherally administered MIF-1 (Pro-Leu-Gly-NH2) and naloxone in blocking the effects of morphine in the tail-flick test were measured across a wide range of five doses in hypophysectomized and intact mice. The presence of the pituitary gland failed to influence the response to MIF-1 or naloxone. Both hypophysectomized and intact mice were significantly affected by these two compounds at doses of 0.01, 0.1, 1.0, and 10.0 mg/kg IP. The greatest effect of MIF-1 occurred at 100 mg/kg, but naloxone was lethal at this dose. Preliminary experiments with other tests showed that at 10 mg/kg, naloxone, but not MIF-1, was effective in preventing the Straub-tail reflex and in precipitating withdrawal-jumping in mice implanted with morphine pellets. Only minimal activity was shown by MIF-1 in preventing blockade of electrically induced contractions of the guinea pig ileum by morphine. Neither compound was active in the frog-righting test. In summary, the results emphasize the differential actions of MIF-1 as an opiate antagonist and demonstrate that the pituitary is not required for their mediation.

Animals↗
PubMed1980

Bone marrow participates in the biosynthesis of human transcobalamin II.

Studies concerning the site of synthesis of the vitamin B12 binding serum protein, transcobalamin II, have been done in various mammalian animals. The actual site of biosynthesis in man has not yet been defined. The finding that bone marrow derived cells release apo-transcobalamin II in the mouse led us to examine the genetic patterns of transcobalamin II in man, both before and after marrow transplantation. A gradual but incomplete transformation of the recipient's transcobalamin II type into donor's type, corresponding to 75% or less of the total activity, was registered in 4 cases. Surprisingly, persistent host-type TC II, in spite of different donor type, was observed in 4 further marrow recipients. We conclude that hematopoietic cells transferred with the transplanted marrow participate in the biosynthesis of human transcobalamin II.

Anemia, Aplastic↗
PubMed1979

[Progress in bone marrow transplantation in acute leukemia and aplastic anemia].

Experience with 17 allogeneic bone marrow transplantation (BMT) patients with refractory acute leukemia is reported. The authors show that it is extremely difficult to cure patients with end stage disease by this procedure. Based on experience that, if performed early, BMT can bring about over 50% potential cures, it is postulated that marrow grafts should be performed much earlier than is done at present. From the results in 45 patients with severe aplastic anemia it is concluded that the majority do not have a defect at the pluripotent stem cell itself. There is disturbed maturation to functional end cells which can be corrected in most instances by ALG, infusion of allogeneic marrow and low dose androgens. BMT between HLA-identical siblings need not cause major problems, but it involves a considerable risk of fatal complications such as irreversible marrow rejection and GvH.

Acute Disease↗
PubMed1979

[Immunosuppression, bone marrow infusion and low dose androgens, successful therapy of severe aplastic anemia].

18 patients with severe aplastic anemia (SAA) but without an HLA-identical sibling were treated by antilymphocyte globulin (ALG) followed by infusion of marrow cells from a semi-compatible family donor. 13 of these received low dose androgens after ALG: 11 (85%) achieved stable remission without transfusion requirement. One patient relapsed after 4 months, one patient with only partial remission died from infection. None of the 4 patients who did not receive androgens after ALG achieved remission. ALG, marrow and low-dose androgens represent a promising therapy for SAA and can be favorably compared with allogeneic bone marrow transplantation.

Adolescent↗
PubMed1979

Pathological cell aggregates in bone marrow cultures from patients with various hematological diseases.

Non-clonal growth of macroscopic cell aggregates in methylcellulose cultures of abnormal marrow is described. They were seen in all patients with Graft-versus-Host Disease, graft rejection, and autoimmune disease presumably directed against hemopoietic cells, we found them in 35% of patients with primary hematological neoplasias and rarely in patients with solid tumors. They were never encountered in 80 healthy controls. The aggregates originated from small cell clumps which sedimented with the "buffy coat" in contrast to normal bone marrow particles. They contained tumor cells, grafted myeloid cells, or target cells of autoimmune disease in association with a widely varying amount of macrophages. Preliminary results suggest that the frequency of macrophages within the aggregates correlates inversely with the aggressiveness of the clinical condition. We propose that appearance of such aggregates in an indicator of immune activation; we expect that further quantitation of the phenomenon will reveal important clinical correlations and provide a model for the study of host defense to "foreign" cells.

Anemia, Hemolytic, Autoimmune↗
PubMed1979

Additional evidence that small amounts of a peptide can cross the blood-brain barrier.

It was determined that an antiserum against delta-sleep inducing peptide (DSIP) required eight of the nine constituent amino acids for antigenic activity. Measurement by this radioimmunoassay (RIA) or DSIP-like material in the rat brain, therefore, would necessarily involve almost the entire molecule present in essentially intact form. Injection of 200 microgram DSIP into the carotid artery of rats resulted in a doubling of brain levels of peptide as measured shortly afterwards by RIA. The brain tissue to plasma ratio of radioactivity in rats injected with labeled DSIP was much higher than that in rats injected with labeled inulin; this suggests that the increased amount of material measured by RIA was not merely trapped in the blood vessels. Thus, the results indicate that a small amount of essentially intact peptide can cross the blood-brain barrier. This could represent one of the mechanisms by which central effects of peripherally injected peptides can be exerted.

Animals↗
PubMed1979

[Bone marrow transplantation in severe aplastic anemia and acute leukemia].

Much progress has been made in allogeneic bone marrow transplantation for severe aplastic anemia (SAA) and acute leukemia (AL). In SAA it was shown that hemopoietic chimerism and apparently permanent cures can be achieved in the majority of patients by conditioning with cyclophosphamide followed by bone marrow transplantation (BMT) from an HLA-identical sibling. The previous transfusion history is crucial for failure or success: untransfused patients do very well while graft rejection is an enormous problem in most polytransfused ones. We have shown that most patients without HLA-identical sibling donors can be adequately helped as well. After conditioning with ALG followed by transfusion of haploidentical marrow and low dose androgens there is partial to complete autologous hemopoietic reconstitution in virtually all patients. This points to the fact that most of these patients have pluripotent hemopoietic stem cells that are intact, but apparently unable to differentiate to mature cells, because they are inhibited by autoimmune mechanisms. The results of BMT in patients with endstage leukemia are modest. New pilotstudies with early marrow grafts, i.e. for ANLL in first remission and for ALL in second remission indicate that with this type of approach potentially over 50% of all patients with HLA-identical siblings can be cured. We recommend that HLA-typing should be performed early in families with SAA and AL and that the possibility of a marrow graft should be seriously considered before the patients have endstage disease. Marrow grafts are technically simple but they may pose enormous problems such as graft versus host reaction (GvH), interstitial pneumonia, graft rejection and leukemic recurrence. Therefore, the procedure should only be performed in highly specialized centers with much knowledge and experience in the immunobiology of bone marrow transplantation.

Acute Disease↗