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W Negendank

Publications and source records attributed to W Negendank.

At least 37 records · Page 2Linked to original sources
PubMed1982

Effects of valinomycin on lymphocytes independent of potassium permeability.

10(-7) M valinomycin affects human lymphocytes in the following manner: (1) it is non-toxic; (2) it inhibits mitogenesis; (3) it causes a reduction in cell ATP; and (4) it causes a marked increase in steady-state Na+ exchange. However, it has a minimal effect on cell ion (K+, Na+, Ca2+, Mg2+) contents and no effect whatever on K+ exchange. Neither the fast nor the slow fraction of steady-state K+ exchange is affected by 10(-7) M valinomycin. The various reported effects of valinomycin on lymphocyte functions cannot be assumed to be due to changes in plasma membrane K+ permeability. The mechanism of the increase in steady-state Na+ exchange, and whether or not it is related to inhibition of mitogenesis, are unsettled issues.

Adenosine Triphosphate↗
PubMed1982

Phase II trial of tamoxifen in metastatic carcinoma of the prostate.

Fifty-one patients with advanced metastatic carcinoma of the prostate were treated with the antiestrogen tamoxifen. Thirty-eight of these patients were refractory to prior hormonal manipulation with estrogens and/or orchiectomy, and five (13%) achieved an objective response (partial regression or stable disease using the National Prostate Cancer Project criteria). Median survival of the responders was significantly longer than that of the nonresponders (P less than 0.05). An additional 13 patients who had not previously received hormonal manipulation were treated with tamoxifen; one partial response and three disease stabilizations were noted. Response was separately evaluated for 15 patients with objectively measurable lesions using standard Phase II response criteria. Only 1/15 (7%) partial response and 3/15 (20%) disease stabilizations were documented. Subjective benefit in terms of significant pain relief was noted in 17/50 (34%) of patients. Toxicity was mild, but two possible "tumor flares" were noted. These results do not support the continued investigation of tamoxifen in advanced carcinoma of the prostate.

Aged↗
PubMed1982

The effect of metabolic inhibition on ion contents and sodium exchange in human lymphocytes.

Lymphocytes depleted of ATP by incubation in iodoacetate (IAA) and nitrogen (N2) lost K and gained Na. Isotopic Na exchange showed a fast fraction and a slower exponential fraction, the latter conventionally assumed to reflect surface membrane properties. The gain of cell Na was not accounted for by a decrease in 22Na efflux in either the slow or the fast fraction. After 3-5 hours, Na efflux increased. These results led us to question the concept that normal cell ion levels are maintained by an ATPase pump and could not be explained by exchange diffusion, co-transport, countertransport, or other inherently dissipative mechanisms. The data are, on the other hand, consistent with the concept that cell ion contents are determined by their relative exclusion from cell water coupled with selective adsorption onto fixed macromolecular anionic sites within the cell. In this view, the IAA,N2-induced rise in cell Na is due to the occupancy of adsorption sites losing K, while the increased isotopic exchange is due to a decreased activation energy for ion-site interaction.

Adenosine Triphosphate↗
PubMed1982

Recognition of human minor alloantigen(s) by cytotoxic lymphocytes in vitro.

Lymphocytes from an extensively transfused patient with aplastic anemia were induced to cytotoxicity against target cells from several HLA-matched siblings by in vitro stimulation with allogeneic cells. Effective stimulating cells shared HLA-B7 with the patient, but not all B7 individuals were effective. An additional factor, which was found to segregate in both the patient's and an unrelated sibship, was also necessary. Segregation of this minor alloantigen, W, was also revealed among the patient's HLA-matched sibs by differential susceptibility to lysis by effectors from the patient. The ratio of six positive to four negative siblings suggests that the antigen difference might be coded by a single locus. Lymphocytes from a normal sib, who like the patient is lacking the minor antigen, could not be induced to cytotoxicity against positive targets. Thus in vivo sensitization of the donor of the responding cells appears to be necessary for the demonstration of the cytotoxic response to the minor antigen in vitro. No correlation was observed between the segregation pattern of W and of known blood group antigens, and no cytotoxic antibody to W was detected in the patient's serum in several trials.

Adult↗
PubMed1982

Temperature-dependence of ATP level, organic phosphate production and Na,K-ATPase in human lymphocytes.

It was previously shown that human lymphocytes maintain a normal accumulation of K+ and exclusion of Na+ between 37 degrees and 10 degrees C., and a significant net accumulation of K+ and exclusion of Na+ at even lower temperatures. The studies reported here show that the level of ATP is near-normal for at least 24 hours between 37 degrees and 10 degrees C., but that ATP synthesis and utilization are progressively and markedly decreased with decreasing temperatures below 37 degrees C. The activities of the membrane Na+- and K+-activated ATPases have typical marked temperature-dependences. Therefore, the normal accumulation of K+ and exclusion of Na+ between 37 degrees and 10 degrees C., and the normal rate of Na+ efflux at these temperatures, do not correlate with properties of the Na+,K+-ATPase or with rates of synthesis and utilization of ATP.

Adenosine Triphosphate↗
PubMed1981

Simultaneous net accumulation of both K+ and Na+ by lymphocytes at 0 degrees C.

Human lymphocytes at 0 degrees C in low Na+ medium accumulate both K+ and Na+ to levels higher than in the external medium. This is not due to an impermeable compartment or a Donnan equilibrium, and is incompatible with the membrane Na+-pump concept. In contrast, it supports prior evidence that ion exchange in lymphocytes is mediated by adsorption onto and desorption from fixed anionic sites within the cell. Additional aspects of ion and water contents of cells in low Na+ medium are described and are explained by this concept.

Adsorption↗
PubMed1980

A critical temperature transition of K+-Na+ exchange in human lymphocytes.

Human lymphocytes were equilibrated for 48 hours at 5-6 mM K+ ex over a range of temperatures between 0 and 37 degrees C, and at 5 degrees C over a range of external K+ levels between 0 and 32 mM. Cell K+ and Na+ contents are normal between 37 and 10 decrees. Below 10 degrees there is a critical thermal transition in ion content centering around 3 degrees C. This and the steep sigmoidal isotherms of K+ and Na+ at 5 degrees C confirm the cooperative nature of ion exchange. At 0 degrees, cell K+ is maintained at a concentration that is seven to eight times that of the external medium. Isotopic K+ influx shows smaller, rapidly-exchanging, and larger, slowly-exchanging fractions. The latter, which correspond to the saturable, sigmoidal components of cell K+, are slowed by decreasing temperature. Although there is a critical temperature transition of K+-Na+ exchange, there is no corresponding transition for isotopic K+ exchange, which has an activation energy of 11.6 kcal/mole. The combined ion content and flux data are readily understood by reference to two major concepts of the association-induction hypothesis: that of rapid solute exclusion from cell water existing in a state of polarized multilayers, and that of solute accumulation limited by adsorption onto and desorption from fixed anionic sites that interact with one another in a critical, cooperative fashion.

Adsorption↗
PubMed1980

Multiple fractions of sodium exchange in human lymphocytes.

Human lymphocytes contain a large, saturable fraction of K+ that exchanges slowly with K+ in the external medium, and a small non-saturable fraction that exchanges rapidly. We determined whether or not Na+ exchanges in a similar manner with external Na+. Cells were pre-equilibrated to ensure absence of net ion movements. Efflux was studied by loading with 22Na and transferring without washing to a non-labeled medium. Influx was studied by transferring to labeled medium and separating large samples of cells at 6,000g. There are fast, intermediate, and slow fractions of Na+ exchange, with half-times of 2, 14, and 120 minutes. At normal external K+, most cells Na+ exchanges rapidly, while at lower external K+ the Na+ that replaces cell K+ exchanges slowly. Parellel sources of fast and slow fractions, such as extracellular ones and subpopulations of cells, were ruled out by simultaneous 42K and 22Na fluxes and by a quantitative analysis of the combined K+ and Na+ content and flux data over a range of external K+ and Na+ levels. Five possible models of ion fluxes occurring in series were considered. Surface matrix, surface binding sites, and cytoplasmic channels with rapid nuclear exchange were eliminated as sources of the fast fractions. Therefore, the fast fractions of K+ and Na+ must reflect the permeability of the surface membrane. This left only two possible sources of the slow fractions. One, a subcellular compartment (e.g., nucleus), was eliminated by the combined content and flux data. We conclude that the slow fractions of ion flux are rate-limited by adsorption onto and desorption from cellular macromolecules. The data support the association-induction hypothesis and are understood by reference to two fundamental concepts: that of rapid solute exclusion from cell water existing in a polarized state; and that of solute accumulation limited by adsorption onto fixed anionic sites within the cell.

Biological Transport↗
PubMed1979

Potassium-sodium distribution in human lymphocytes: description by the association-induction hypothesis.

Human lymphocytes were equilibrated for 48 hours over a wide range of external potassium levels, and their contents of potassium, sodium, and water determined. As external potassium rose from zero, cell potassium rose steeply in a sigmoidal fashion, reached half-saturation at 0.4 mM esternal potassium, and then saturated at 129 mmoles/kg cells. The saturable cell potassium exchanged mole-for-mole with sodium. Analysis of the saturable components by a statistical-mechanical adsorption model demonstrated a cooperative intraction between sites determining equilibrium potassium-sodium distribution. Superimposed upon the saturable fraction of cell potassium was a smaller one that was non-saturable with increasing external potassium to at least 64 mM, and that, when expressed as mmoles/liter cell water, existed in a ratio to external potassium of 0.6. The results strongly support the association-induction hypothesis, which predicts a small non-saturable component of ions determined by exclusion from oriented cell water and a cooperative interaction between sites throughout the cell that associate with potassium or sodium.

Adsorption↗
PubMed1979

Rate of potassium-sodium exchange by human lymphocytes: prediction of the cooperative adsorption model.

The equilibrium parameters of potassium-sodium distribution in human lymphocytes, determined experimentally in the preceding study (Negendank and Shaller, '79), were incorporated into a stochastic treatment of the cooperative adsorption model in order to predict the kinetics of "active" potassium-sodium exchange. The rate of uptake of potassium, in potassium-depleted, sodium-loaded cells, is complex and deviates markedly from simple exponential functions. The sigmoid form of the exchange data closely followed the predicted curve. This result enhances one's confidence in the usefulness and applicability of the cooperative adsorption model, and adds further support to the association-induction hypothesis as a coherent theory of cell physiology.

Adsorption↗
PubMed1979

Fast and slow fractions of K+ flux in human lymphocytes.

Potassium influx and efflux were studied in human peripheral blood lymphocytes equilibrated over a wide range of external K+ levels. The absence of a net ion movement throughout the flux study was established, trapped space was measured with polyethylene glycol, and cells were separated from incubation media without exposure to any washing solution. There are both rapid and slow cellular fractions of 42K influx and efflux, and half-times of exchange of around 2 minutes, and 400 minutes, respectively. The rapid component is identical in magnitude to the smaller non-saturable component of cell K+, while the slow component is identified with the larger, sigmoidal, saturable component of cell K+ that was previously shown to follow a cooperative adsorption isotherm. These results support the association-induction hypothesis, which predicts (a) a rapid fraction of K+ flux due to equilibration of ion within cell water existing in a state of polarized multilayers, and (b) a slower component of K+ flux limited by adsorption onto, or desorption from, fixed anionic sites existing throughout the cell. K+ influx, as a function of external K+, showed a triphasic relation with a peak around 1 mM K+ex, then a trough around 4mM K+ex, and then a gradual rise. This relation was readily explained, in terms of the association-induction hypothesis, by the cooperative interaction between, and ion occupancy of, fixed anionic sites that adsorb K+ or Na+.

Cell Compartmentation↗
PubMed1979

Human monocyte-lymphocyte interaction and its enhancement by levamisole.

We investigated the role of monocyte-lymphocyte interaction in the transformation of human peripheral blood lymphocytes by the mitogen concanavalin A (Con A). Human monocytes were separated from lymphocytes and were transiently exposed to Con A. The Con A-pretreated monocytes were able to subsequently bind autologus lymphocytes by a process that was selective for T cells. This interaction required the initial presence of Con A at the monocyte surface, and became independent of surface bound ligand after 72 hr. Levamisole, an agent thought to facilitate the participation of monocytes in the cellular immune response, enhanced the binding of lymphocytes to monocytes at low concentration of Con A (5--10 micrograms/ml). Levamisole did not lead to mitogen independent lymphocyte binding. The association between lymphocytes and Con A-pretreated monocytes resulted in the mitogenic transformation of lymphocytes in the absence of soluble Con A in the medium. These results suggest that, in addition to any possible soluble mediators, direct lymphocyte-monocyte contact is required for optimal mitogenic transformation. This T-cell-monocyte interaction over time becomes independent of cell-surface mitogen. The ability of levamisole to enhance this interaction may explain levamisole's capacity to stimulate lymphocyte proliferation.

Adult↗
PubMedDate not supplied

Studies of human tumors by MRS: a review.

The literature describing 31P, 1H, 13C, 23Na and 19F MRS in vivo in human cancers is reviewed. Cancers have typical metabolic characteristics in 31P and 1H MRS including high levels of phospholipid metabolites and a cellular pH more alkaline than normal. These alone are not specific for cancer but are diagnostic in appropriate clinical settings. Some metabolic characteristics appear to be prognostic indices and correlation with treatment response is emerging as an important potentially cost-effective use of MRS in oncology. 19F MRS examines pharmacokinetics of 5-fluorouracil and by demonstrating its retention predicts response of a cancer to treatment. Current needs include improvement of diagnostic specificity by use of techniques like multivoxel MRS, proton decoupling of 31P, short echo time and fat-suppressed 1H MRS, 13C MRS direct or via 1H-observe, and statistical analysis of multiple spectral features. Trials in large populations in well defined clinical settings are needed to determine if MRS can provide independent prognostic indices useful in cancer management.

Brain Neoplasms↗
PubMedDate not supplied

Tamoxifen in refractory metastatic carcinoma of the prostate.

Thirty-one patients with advanced metastatic carcinoma of the prostate were treated with the antiestrogen tamoxifen. Of these patients, 29 were refractory to prior hormonal manipulation with estrogens and/or orchiectomy and five achieved an objective response (partial regression of stable disease using National Prostatic Cancer Project criteria). Median survival of the responders was significantly longer than that of the nonresponders (P < 0.05). Two additional patients who had not previously received hormonal therapy both responded, for an overall response rate of 23% (seven of 31 patients). Toxicity was minimal and no tumor flares were reported. These preliminary results support the further clinical trial of tamoxifen in advanced cancer of the prostate.

Adenocarcinoma↗