Search PubMed⌕ Search

Biomedical subjects

R Keller

Publications and source records attributed to R Keller.

At least 253 records · Page 14Linked to original sources

Induction of interleukin 1 secretion and of tumoricidal activity in macrophages are not closely related phenomena.

Rat bone marrow-derived mononuclear phagocytes (BMM phi), induced to differentiate in vitro and homogeneous with respect to the cell lineage, were interacted with various macrophage-activating agents. The effect of these agents on the secretion of interleukin 1 (IL 1) activity and on the development of tumoricidal capacity was comparatively assessed. The findings show that IL 1 secretion is considerably enhanced by macrophage-activating factor and by recombinant interferon-gamma but remained unaffected or was even suppressed by heat-killed C. parvum or Listeria monocytogenes. In contrast, lymphokines as well as C. parvum and Listeria were similarly potent in inducing in BMM phi a tumoricidal state. The findings indicate that induction of IL 1 secretion and of tumoricidal activity are not necessarily closely linked phenomena.

Animals↗

Unusual cardioactive peptide (CCAP) from pericardial organs of the shore crab Carcinus maenas.

An unusual crustacean cardioactive peptide (CCAP) from the pericardial organs of the shore crab Carcinus maenas has been purified to homogeneity by a two-step reversed-phase HPLC procedure. Manual microsequencing using the 4-(N,N-dimethylamino)azobenzene 4'-isothiocyanate/phenylisothiocyanate double-coupling technique and automated gas-phase sequencing of the oxidized peptide revealed that CCAP is a nonapeptide (M(r) 957) of the sequence Pro-Phe-[unk]Cys-Asn-Ala-Phe-Thr-Gly-Cys-NH(2). We have confirmed the sequence by chemical synthesis of the C-terminally amidated and nonamidated forms of the peptide. The presence of the amide group was indicated by lack of susceptibility to carboxypeptidase A and Y treatment and was confirmed by the observation that the native CCAP comigrated with the amidated synthetic peptide on HPLC. Native and synthetic CCAP displayed high accelerating activity on a semi-isolated crab heart preparation, whereas the nonamidated synthetic peptide was of much lower potency. The effect of CCAP was both inoand chronotropic. The two pericardial organs of one animal yielded 30-40 pmol of extractable CCAP. Its sequence does not resemble that of any known neuropeptide. However, a "mirror-image" similarity to vasopressin is conspicuous.

Journal Article↗

Acute headache in childhood: a case of sphenoid sinusitis.

A case of sphenoid sinusitis is presented. This case exemplifies the need to consider sinusitis in the differential diagnosis of severe headache, even without the accompanying signs and symptoms of sinusitis. The clinical, presentation, diagnostic work-up, potential complications, and treatment of sphenoid sinusitis are reviewed.

Acute Disease↗

Cell behaviour during active cell rearrangement: evidence and speculations.

The cell behaviour and motility underlying cell rearrangement during gastrulation in amphibian and sea-urchin embryos are discussed. In particular, the cell behaviour of deep (non-epithelial) and epithelial cell populations that undergo cell rearrangement is compared and contrasted. Deep cell rearrangement in Xenopus laevis involves both convergence of cells towards the future dorsal midline and simultaneous axial extension of the mesodermal cell mass. Time-lapse cinemicrography and scanning electron microscopy suggest that asynchronous, repetitive motions of individual deep cells, involving local extensions and retractions of their margins, may provide the motive force for rearrangement. Such protrusive activity may be guided by local differences in cell-cell contacts in the marginal zone. Epithelial cell rearrangement in the sea-urchin embryo both elongates the archenteron and simultaneously closes the blastopore. Cell rearrangement is accompanied by stage-specific changes in protrusive activity and cell shape of the basal surfaces of cells in the wall of the gut rudiment, in contrast to the apical surfaces, which show little activity. These basal protrusions may be involved in the rearrangement process.

Animals↗

Pharmacological profiling of cardiovascular agents in healthy volunteers by means of non-invasive methods.

In a placebo-controlled study the hemodynamic effects of single doses of oxprenolol, metoprolol, prenalterol, phentolamine, nifedipine, nitroglycerin, angiotensin II and frusemide have been investigated in 9 healthy volunteers by means of the combined measurement of heart rate, blood pressure, pre-ejection period (systolic time intervals) and stroke volume (impedance cardiography) in the supine and tilted positions (70 degrees). Each cardiovascular agent exhibited its characteristic pharmacodynamic profile, which allowed a clear-cut discrimination. The effects of oxprenolol and metoprolol, however, could not be distinguished by this procedure. The pre-ejection period, although not a very specific parameter, proved to be most sensitive to the pharmacological interventions, whereas stroke volume was less often influenced. It is concluded that the proposed selection of non-invasive parameters is a very suitable and simple means for early cardiovascular drug testing in man.

Adrenergic beta-Agonists↗

Aortic endothelial cell proteoheparan sulfate. II. Modulation by extracellular matrix.

The effects of extracellular matrix components on proteoheparan sulfate biosynthesis was studied for bovine aortic endothelial cells in tissue culture. When the cells were maintained on a variety of different purified components of the extracellular matrix, the cells expressed the same three species of proteoheparan sulfates as the cells cultured on tissue culture plastic (HS I, HS II, and HS III). However, the amounts of the three species recovered from the tissue culture medium were found to be dependent on the substrate on which the cells are grown as well as on other factors. In comparison with plastic, much less HS I was found in the medium of cells maintained on substrates containing diverse matrix molecules, whereas the amounts of HS II and HS III essentially remained the same. In contrast, when bovine aortic organ cultures were analyzed under pulsatile flow, marked differences in the profile of proteoheparan sulfate biosynthesis were observed: HS I was found exclusively associated with the plasma membrane of the endothelial cells; HS II was localized only to the subendothelial matrix; and HS III represented the only proteoheparan sulfate species in the medium. This distribution is consistent with polarized secretion and deposition into the subcellular matrix of HS III and retention of HS I in the plasma membrane in the organ culture situation, a biosynthetic phenotype which can only be approximated at best by maintaining the endothelial cells on a substrate other than plastic. When aortic media (devoid of endothelial cells) was placed in organ culture, no HS III could be detected, which suggested that the vascular endothelial cell is the major cell type responsible for its synthesis in organ culture. Thus, the extracellular matrix, depending upon its composition and organization, may play an important role in stabilizing cell polarity and thereby contribute to maintenance of the differentiated phenotype appropriate for the endothelial cell.

Animals↗

Laser Doppler flowmetry, a reliable technique for measuring pharmacologically induced changes in cutaneous blood flow?

Laser Doppler flowmetry (LDF) affords a reliable non-invasive method of investigating acute changes in total cutaneous perfusion. However, the reproducibility of measurements of resting blood flow is considered to be poor. Therefore, the potential use of LDF to monitor pharmacological influences on cutaneous perfusion over time may be limited to the investigation of drug-induced changes of the response pattern to standardized provocation procedures. The present study was undertaken to evaluate the reproducibility of cutaneous vasomotor reflexes induced by various test stimuli. Measurements were made in the morning and in the afternoon of the same day at two different skin sites (finger-tip and forearm) in six healthy subjects. Each of the following six interventions induced highly reproducible decreases of total cutaneous flow: Deep inspiration, Vasalva manoeuvre, venous occlusion, arrest of arterial blood flow (followed by reactive hyperaemia), passive head-up tilting and a cold pressor test. The decrease in blood flow was more pronounced at the finger-tip except after venous occlusion. During the cold pressor test, skin perfusion was more persistently reduced at the finger-tip than at the other site. The anatomical and functional differences in the skin between the finger-tip and the forearm may also explain the absence of reactive hyperaemia at the finger-tip. Considering the excellent reproducibility of the resting baseline values and of the changes in total blood flow after standardized provocation tests within the same day, it seems possible that LDF could be a suitable method for the short-term investigation of drug effects on circulation. The long-term day-to-day reproducibility of both baseline blood flow and vasomotor reflexes remains to be further clarified.

Adult↗

Aortic endothelial cell proteoheparan sulfate. I. Isolation and characterization of plasmamembrane-associated and extracellular species.

Proteoheparan sulfate biosynthesis was studied in cultured bovine aortic endothelial cells by means of pulse and pulse-chase experiments and subcellular fractionations. Three proteoheparan sulfate species were found in the medium. The major species, which the authors have called HS I, appeared in the medium only after an initial lag period and was also found associated with the plasma membrane. The other two (HS II and HS III) appeared in small amounts in the medium at early time points. At later times these were not readily observed because the large amounts of HS I present in the medium. The major medium species, HS I, appeared to be composed of approximately four heparan sulfate chains of approximately 35,000 daltons and a core protein of approximately 55,000 daltons apparent molecular weight. HS I appeared to be homogeneous by gel filtration on Sepharose CL 2B and 6B and elution from DEAE Sephacel, electrophoresis on Nu-Sieve agarose, and CsCl density centrifugation. After digestion with heparinase the core protein appeared to be homogeneous by S-200 Sephacel chromatography. HS I was also found associated with plasma membrane fractions of the cultured bovine aortic endothelial cells, and antisera raised against it stained epithelial and endothelial cells in patterns consistent with a cell surface localization. Of the other two species found in the medium, one (HS II) also appeared to be a component of the cell layer. This species appeared to contain approximately four heparan sulfate chains of approximately 20,000 daltons apparent molecular weight. Antisera raised against a similar molecule produced by HR 9 cell cultures stained basement membranes intensely, supporting the subcellular matrix localization of this molecule. The third species (HS III) was detected in culture medium only and apparently contained two heparan sulfate chains of approximately 20,000 daltons apparent molecular weight. These results support the concept of multiple endothelial cell proteoheparan sulfate species which exhibit differences in structure and localization and possibly diverse specialized functions.

5'-Nucleotidase↗

Isolation and characterization of basement membrane and cell proteoheparan sulphates from HR9 cells.

The mouse teratocarcinoma cell line HR9 was investigated for proteoheparan sulphate production. Four species of proteoheparan sulphate molecules were isolated and purified to homogeneity. The proteoheparan sulphate isolated from the tissue-culture medium contains four heparan sulphate side-chains of 25 kDa each, and its core protein has an approximate molecular mass of 50 kDa. The proteoheparan sulphates associated with the cells were separated into three individual species: cell proteoheparan sulphate I exhibits structural characteristics which are very similar to the proteoheparan sulphate isolated from the tissue culture medium; cell proteoheparan sulphates II and III contain one heparan sulphate chain of 25 kDa and 20 kDa, and core proteins of approximately 30 kDa and 25 kDa respectively. Antisera, raised against the medium form, react specifically with basement membranes in various tissues by immunofluorescence. This staining pattern was compared to the pattern observed with an antiserum which we have obtained to a proteoheparan sulphate species isolated from the plasma membrane of bovine aortic endothelial cells. The structural and immunological data suggest that basement membrane and plasma membrane proteoheparan sulphates are different biosynthetic products and are not directly related to each other.

Amino Acids↗

Firm persistent binding between activated macrophages and tumor cells is not a prerequisite for the mediation of cytolysis.

The present study seeks to reassess the roles of macrophage activation and persistent firm binding to tumor cells as a prerequisite for tumoricidal activity. To this end, macrophage effector populations from various tissues, expressing diverse functional activities, were made to interact in vitro with different suspension tumor cell lines. The resultant binding and cytolytic effector cell capacities were determined. Macrophage activation appears to be an absolute prerequisite for binding and for killing of tumor cells. Activated macrophages firmly bind and form clusters with D-12 rat fibrosarcoma cells, which are relatively resistant to macrophage-mediated tumoricidal action. In contrast, P-815 murine mastocytoma cells, highly susceptible to the lytic activity of macrophages, bind rather poorly with activated macrophages and do not form clusters. Since susceptible target cells are readily killed by activated rat macrophages in the absence of persistent firm contact, it appears that firm binding and killing are not causally related events.

Animals↗

T-cell chronic lymphocytic leukemia with pure red cell aplasia: laboratory demonstration of persistent leukemia in spite of apparent complete clinical remission.

A 40-year-old woman presented with splenomegaly, macrocytic anemia, and red cell aplasia. Although lymphocytosis was absent in the peripheral blood, large atypical lymphoid aggregates were present in the bone marrow. Splenectomy resulted in partial remission of red cell aplasia, but a gradual increase in the number of peripheral blood lymphocytes followed during the next 36 months. Flow cytometric analysis demonstrated that the majority of these peripheral blood lymphocytes had suppressor, natural killer T-cell phenotype. No other treatment was given until red cell hypoplasia worsened 42 months after initial presentation. Repeat bone marrow evaluation again demonstrated severe erythroid hypoplasia and large abnormal lymphocytic infiltrates. Cyclophosphamide given for 8 months resulted in complete resolution of the red cell aplasia and complete clinical remission of CLL. However, flow cytometric analysis revealed persistent increase in bone marrow T-cells, and bone marrow co-culture studies demonstrated residual ability of peripheral blood mononuclear cells to inhibit erythropoiesis in vitro, suggesting that residual, clinically undetectable leukemia persists in spite of complete clinical remission.

Adult↗

[Air pollution and lung diseases in adults].

Short-time exposure to air pollutants and in particular to sulfur dioxide, nitrogen oxides and photochemical oxidants may cause respiratory symptoms similar to acute bronchial asthma. In healthy adults however the concentrations required to evoke significant bronchial obstruction lie still above the level of atmospheric air pollution usually observed in our country. In contrast patients with preexisting pulmonary diseases or with impaired bronchopulmonary defense mechanisms may show harmful reactions even at concentrations which actually occur in urban and rural atmospheres. In addition there is evidence of on increased prevalence of chronic obstructive pulmonary diseases in countries with high chemical pollution indicating that long-term exposure of ambient air pollution may cause chronic illness as well. Since air pollution is accepted to produce adverse health effects, emergent efforts are required to improve air quality in order to avoid further injuries in man.

Adult↗

Induction, maintenance, and reinduction of tumoricidal activity in bone-marrow-derived mononuclear phagocytes by macrophage-activating lymphokines.

Rat bone-marrow-derived mononuclear phagocytes, induced to differentiate in vitro from precursors and virtually homogeneous with respect to the cell lineage, were the source of effector cells. These effector cells do not manifest spontaneous cytolytic activity in the resting state, but readily acquire marked long-term tumoricidal activity upon incubation with macrophage-activating lymphokines (MAF). MAF-induced tumoricidal activity of bone marrow-derived effector cells decays rapidly. However, in sharp contrast to tissue macrophages, bone marrow-derived mononuclear phagocytes retain in vitro responsiveness to a primary exposition to MAF over a period of several weeks, postcytolytic mononuclear phagocytes recover reactivity to MAF after a variable time interval.

Animals↗

The effects of aphidicolin on morphogenesis and differentiation in the sea urchin embryo.

Aphidicolin, an inhibitor of DNA polymerase alpha, blocks DNA synthesis and cell division in sea urchin embryos. The effects of this inhibition appear to be stage dependent. Blastulae treated with aphidicolin before the thickening of the vegetal plate undergo developmental arrest prior to gastrulation. The extent of inhibition of DNA synthesis varies from 60 to 93% in these embryos. However, when aphidicolin is added after the vegetal plate has thickened, development continues normally through pluteus formation, even though DNA synthesis is inhibited by greater than or equal to 90% and cell division has ceased. These observations indicate that, from the vegetal plate stage onward, morphogenesis and overt differentiation are independent of DNA synthesis and cell division.

Animals↗

Amnesia or fugue state: a diagnostic dilemma.

We report the case of a 16-year-old boy whose presenting symptoms were total retrograde amnesia. After finding no evidence for organic causes, including toxic-metabolic derangements, epilepsy, encephalitis, vasculitis, trauma, or CNS neoplasm, it was determined that the child experienced a psychogenic fugue state with a spontaneous recovery in memory over several days. Although rare, fugue state should be considered in the differential diagnosis of amnesia.

Adolescent↗