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Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 469 records · Page 26Linked to original sources
PubMed1982

Regulation of water intake.

Here we have reviewed mainly the cerebral regulation of water intake and its relationship with the regulation of the water-retaining antidiuretic hormone (ADH). Much new information of obvious interest has been gained by experiments in conscious animals, by studies in healthy humans, and by clinical investigations. Of particularly great value has been the development of a sensitive radioimmunoassay for determination of plasma ADH (59). The sketchy picture that emerges in light of this new information is as follows. The osmotic regulation of water intake and ADH secretion is exerted by juxtacerebroventricular sensors apparently mainly located on the anterior border of the third ventricle. These sensors may be accessible both to CSF-borne and blood-borne stimuli and inhibitors, and their activity seems to be correlated to the Na concentration of the ECF rather than to its tonicity. A less sensitive volume regulation of water intake and ADH secretion is effectuated by cardiovascular distention and pressure receptors monitoring the effective circulating blood volume, and in severe volume depletion states also by the renin-angiotensin system (RAS). Afferent impulses from the cardiovascular receptors exert a tonic inhibition of the ADH release by acting upon its final neuronal link (the cells of the supraoptic and paraventricular nuclei). Afferent inflow from these receptors also inhibits thirst to some extent, perhaps by preventing at some synaptic level information from cerebral "thirst" sensors from reaching other parts of the brain where the information is converted into a conscious urge to drink. Therefore, increased cardiovascular receptor activity becomes manifested as elevated osmotic thresholds for ADH liberation and thirst. Severe volume depletion may induce RAS hyperactivity to such an extent that generated angiotensin II stimulates the ADH release and water intake. Demonstrated cerebral Na/angiotensin interaction suggests that this may occur via an angiotensin-induced lowering of the stimulus threshold for the sensors involved in the osmotic control of water balance. Cerebral damage affecting the sensors responsible for the osmotic regulation of water intake and ADH release may result in hypo- or adipsia associated with latent diabetes insipidus, and is apparently the ultimate cause of "essential" hypernatremia. This fragmentary outline of the cerebral control of water intake is based to a considerable extent upon circumstantial evidence, and is for that reason speculative on many points.

Drinking↗
PubMed1982

Benign paroxysmal vertigo in childhood.

Fifteen children with a syndrome called benign paroxysmal vertigo are presented. This syndrome is characterized by attacks of vertigo of sudden onset lasting a few minutes and in extreme cases several hours or even up to 2 days. Additional symptoms are pallor, sweating, vomiting and nystagmus. Consciousness is not impaired. The attacks usually occur in the first 4 years of life. They are recurrent, the appearance varying from several times a week to once a year, and they may cease spontaneously after only months but usually years. The most important differential diagnoses are epilepsy and posterior fossa tumour. The etiology is unknown, but there may be a vascular disturbance affecting the posterior cerebral circulation with secondary disturbances of the vestibular nuclei.

Child↗
PubMed1982

Inhibition of in vitro granulopoiesis by autologous allogeneic human NK cells.

This study demonstrates the ability of human NK cells to inhibit in vitro granulopoiesis of autologous and allogeneic BM cells. NK lytic activity and GM-CFC inhibition was present among nonstimulated lymphocytes from healthy donors and could be increased by treatment of PBL with IFN. Both the cytotoxic NK cells and the GM-CFC inhibitory cells could be enriched for among nonadherent, low-density cells. High-density cells were not cytotoxic, only inhibitory to a small extent, and could become neither cytotoxic nor more inhibitory after IFN treatment. In contrast, low-density cells showed an increased cytotoxic and GM-CFC inhibitory capacity after IFN treatment. The NK mediated GM-CFC inhibition was dependent on cell contact with BM cells, increased with longer preincubation times, and was most efficient against 7-day GM-CFC as compared with 14 day GM-CFC progenitors. In conclusion, these data provide new information about the human NK cell as a potent inhibitor of in vitro granulopoiesis and also as a possible regulator of hematopoiesis in vivo.

Binding, Competitive↗
PubMed1982

Significance of cellular pharmacokinetics for the cytotoxic effects of daunorubicin.

The effect of free and DNA-linked daunorubicin on the colony-forming ability of granulocyte-macrophage committed stem cells and spleen colony-forming cells (i.e., multipotent stem cells) from normal mice has been studied in vitro and in vivo. After incubation of bone marrow cells in short-term suspension cultures, both committed and multipotent stem cells were more sensitive to the free drug than to the DNA complex, whereas the reverse was found in vivo after i.v. injection. However, when the in vitro cell-killing effect was related to the cellular retention of daunorubicin, no difference in activity was found between free and DNA-linked drug. Incubation of the bone marrow cells with a higher drug concentration for a shorter time resulted in a considerably lower cell survival than incubation with a lower concentration for a longer time, the intracellular exposure dose being the same. When the in vivo cell survival was related to the cellular retention of daunorubicin, the DNA complex was slightly more toxic than free drug, which can be explained by the higher peak concentration obtained. The results obtained with committed granulocytic stem cells and multipotent stem cells were comparable. Thus, the observed discrepancy between the in vitro and in vivo toxicity of free and DNA-linked daunorubicin can be explained by the differences in cellular retention of daunorubicin under these two conditions; i.e., the DNA complex probably acts as a slow-release preparation of daunorubicin. The results also demonstrated for the first time the importance of the peak concentration of daunorubicin in the target cells and indicate an important role of dose scheduling for the cytostatic effect of the drug.

Animals↗
PubMed1981

Glucocorticoid receptor concentrations and terminal transferase activity as indicators of prognosis in acute non-lymphocytic leukaemia.

Activity of terminal deoxynucleotidyl transferase (TdT), adenosine deaminase, and 5'nucleotidase and the cellular concentration of glucocorticoid (dexamethasone) receptor were determined in 25 patients with acute non-lymphocytic leukaemia. All patients were treated according to a common protocol. Increased activity of TdT (greater than 0.1 unit/microgram DNA) was found in 11 patients. This group of patients was shown to have higher remission and survival rates (p = 0.06) compared with patients with low activity of TdT. The glucocorticoid receptor concentration of the leukaemic blast cells ranged from 0 to 0.94 fmol/microgram DNA. Thirteen patients had blast cells with a glucocorticoid receptor concentration over 0.22 fmol/microgram DNA. These patients had significantly increased remission and survival rates (p = 0.006) compared with those with a low receptor concentration. This finding cannot be explained by a difference in sensitivity to glucocorticoids since these were not used as therapeutic agents. Adenosine deaminase and 5'nucleotidase activities both varied within two orders of magnitude. No correlation could be found between activities of these enzymes and remission or survival rate. These results show that measurements of TdT activity and the glucocorticoid receptor concentration yield valuable prognostic information in acute non-lymphocytic leukaemia.

5'-Nucleotidase↗
PubMed1981

Pharmacokinetics of daunorubicin after administration as free drug or as DNA complex in leukemic patients.

An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug.

DNA↗
PubMed1981

Adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells in vitro: differences in adhesive capacity among strains isolated from subjects with otitis media, septicemia, or meningitis or from healthy carriers.

A method was developed to study the adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells. Epithelial cells from healthy persons, pneumococcal strains from patients with otitis media, meningitis, or septicemia, and pneumococcal cells from the nasopharynx of healthy carriers were used. Adhesion was found to be influenced by changes in the bacterial incubation medium and growth phase, the concentration of bacteria and epithelial cells, the epithelial cell donor, the incubation time and temperature, and the pH and osmolarity of the incubation medium. Pretreatment of bacteria with heat, Formalin, or trypsin decreased adhesion. The highest adhesion was obtained when 10(9) bacteria cultivated for 18 h in streptococcus cultivation broth were added to 10(4) pharyngeal cells and incubated at 37 degrees C for 30 min. S. pneumoniae strains from patients with frequent episodes of otitis media and strains from healthy carriers had the highest adhesion values; septicemia and meningitis strains had the lowest. The capsular polysaccharide type did not determine the adhesive capacity of the strains, but otitis strains belonging to the capsular types often associated with otitis media adhered in high numbers. Adhesion may be important for pneumococci colonizing the nasopharynx or inducing otitis media.

Carrier State↗
PubMed1981

Differences in the plasma kinetics of daunorubicin in normal and leukemic rats.

The plasma pharmacokinetics of the anthracycline drug daunorubicin in doses of 1 and 10 mg/kg body weight were compared in normal and leukemic inbred Sutton-August rats (50-70 x 10(9) leukemic cells/1 blood). The area under the plasma concentration versus time curve was about 25 times larger in the leukemic rats at both dose levels. The data indicate that daunorubicin has a lower volume of distribution in leukemic rats as compared with normals. The large reduction in plasma clearance of daunorubicin in the leukemic rats can to some extent be explained by impairment of hepatic and renal functions but the results indicate that the leukemic state per se was of importance for the observed pharmacokinetic differences. This finding may be of importance for the treatment of patients with a high leukemic cell load, since higher retention of the drug in the central compartment leads to lower concentrations in poorly vascularized tissues, which favours the development of resistant leukemic cell clones.

Animals↗