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T Klein

Publications and source records attributed to T Klein.

At least 217 records · Page 12Linked to original sources
PubMed1986

Quantitative structure-activity relationships and molecular graphics in ligand receptor interactions: amidine inhibition of trypsin.

Quantitative structure-activity relationships have been formulated for four sets of amidine inhibitors of trypsin. The quantitative results from these equations are compared with qualitative models constructed from the X-ray crystallographic coordinates of a benzamidine bound to trypsin. The good agreement between the mathematical and graphics models provides further support for the use of substituent constants and regression analysis in the study of enzyme-ligand interactions.

Amidines↗
PubMed1985

Driver's decision process on termination of the green light.

The paper describes the background and evaluates the effectiveness of a flashing green phase just before the amber leading to red phase in the traffic signal cycle. This type of signal sequence, practiced in Israel and a few other countries, was thought to provide drivers with useful information which should lead to better stop or go decisions. However, accident analysis studies have shown an increase in collisions following the introduction of a flashing green. A laboratory simulation study designed to explain the accident findings was conducted. It was found that the flashing green elicited from the drivers an earlier decision response and a higher number of inappropriate stopping decisions, particularly close to the intersection. The pattern of stopping and crossing decisions in the flashing green program suggests more friction between stopping and nonstopping vehicles and, therefore, a higher likelihood of front-rear collisions compared to a regular program.

Accidents, Traffic↗
PubMed1985

Estrogen and progesterone receptors in the uterus of the vervet monkey.

Experimental conditions for the optimal measurement of estrogen (ER) and progesterone (PR) receptors in normal vervet monkey (Cercopithecus aethiops pygerythrus) uteri are described. The uteri of this primate were found to contain relatively high concentrations of both ER and PR. Levels of ER ranged from 151 to 822 femtomoles per mg protein (mean for group assayed is 327 +/- 165 femtomoles per mg protein). PR assays were performed on the same cytosols and the levels ranged from 444 to 2267 femtomoles per mg protein (mean of 1285 +/- 511 femtomoles per mg protein). Mean Kd values for the ER- and PR-ligand complexes were found to be 3.15 +/- 1.4 X 10(-10)M and 2.38 +/- 0.2 X 10(-9)M respectively, within the group analysed (n = 21). The ratio of PR to ER varied between 1.1 and 13.1 with a mean of 4.5 +/- 2.4. Ligand specificity studies revealed that [3H]-17 beta-estradiol binding to the ER could only be inhibited by estrogens or estrogen analogues. The PR however exhibited an affinity for a wider range of ligand types. In low ionic strength buffers both ER and PR sedimented as approximately 8S type molecules in the presence or absence of 10mM sodium molybdate. Both receptors dissociated into smaller components, following a short exposure to 0.4 M KCl and subsequent centrifugation in a gradient containing 0.4 M KCl.

Animals↗
PubMed1985

Reversibility of the stabilization effect of sodium molybdate on uterine estrogen and progesterone receptors of the vervet monkey.

Sodium molybdate affected the stability of vervet monkey (Cercopithecus aethiops pygerythrus) uterine estrogen (ER) and progesterone (PR) receptors. Yields of receptors were invariably higher (20-40%) when cytosols were prepared in the presence of 10mM sodium molybdate. No changes were observed in the binding affinities for the natural ligands as reflected in dissociation constants. Receptor-ligand association at 0 degrees C and 20 degrees C was not affected in the presence or absence of molybdate. Stability studies at 37 degrees C indicated both receptors to be more resistant to inactivation in the presence of molybdate. Dissociation of ER and PR was biphasic, indicating the existence of slow (SDC), as well as fast dissociating (FDC) complexes. Rate constants of dissociation were significantly affected by the presence of sodium molybdate. Although no significant changes in the sedimentation coefficients were observed, marked differences in the actual gradient profiles could be illustrated in the presence or absence of sodium molybdate. Observed effects could only be partially reversed in sedimentation dialysis experiments. Proteolytic inhibitors phenylmethylsulfonylfluoride (PMSF) and leupeptin had no inhibitive effect on the molybdate stabilization of ER and PR.

Animals↗
PubMed1985

[Circulating immune complexes in breast cancer].

The occurrence of circulating immune complexes (CIC) was investigated in serum samples from 139 patients with breast cancer, using the 125I-C1q binding test. In the 85 cases of regional forms, the level of Clq binding activity did not appear to be correlated with the clinical TN stage, nor with the local treatment of the tumor. Conversely it was clearly elevated in the 13 cases of inflammatory breast tumors, and the decrease of CIC at the post-chemotherapy, but pre-surgical stage may involve the inflammatory signs in this augmentation of CIC. Frequency of occurrence and levels of CIC were slightly increased in the 41 metastatic breast cancer patients when compared to the cases of local breast carcinoma. In the disseminated forms, increase, no change, or decrease of CIC levels showed a poor correlation to progression, stabilisation, or improvement of the disease. CIC seems to be of slight prognostic value in breast cancer with local forms, but regarding progression of the disease, metastatic breast cancer patients with elevated CIC did not prove to be unfavorable group. So far, CIC did not appear to be a tumor marker or an evident prognostic factor of clinical relevance in breast cancer. Assays for antigen-specific CIC might be of greater clinical significance, in breast cancer, than the antigen non specific assays available at present.

Acute Disease↗
PubMed1985

A quantitative structure-activity relationship and molecular graphics study of carbonic anhydrase inhibitors.

A quantitative structure-activity relationship (QSAR) (log K = 1.55 alpha + 0.64 log P - 2.07I1 - 3.28I2 + 6.94) has been formulated for the binding of a set of substituted benzenesulfonamides to human carbonic anhydrase. The binding constant (K) are from the studies of King and Burgen [Proc. R. Soc. Lond. B. 193:107-125 (1976)], sigma is the Hammett electronic substituent constant, P is the octanol/water partition coefficient, and I1 and I2 are indicator variables for meta and ortho substituents, respectively. The negative coefficients with the indicator variables suggest steric hindrance by these substituents in contrast to para substituents. Qualitative features of the QSAR are correlated with a color stereomolecular graphics model of the enzyme-inhibitor complex which was constructed from the X-ray crystallographic coordinates of the enzyme.

Carbonic Anhydrase Inhibitors↗
PubMed1984

Legionella pneumophila-induced blastogenesis of murine lymphoid cells in vitro.

Legionella pneumophilia antigen preparations, either killed whole cell vaccine, a soluble sonic extract, or a purified large-molecular-weight somatic antigen, stimulated blastogenic responses by splenocytes from both normal and Legionella-sensitized mice. Graded amounts of the bacterial preparations, when added to cultures of normal spleen cells, resulted in increased uptake of thymidine into cellular DNA, indicating that the preparations were mitogenic for normal mouse splenocytes. Spleen cells from mice injected with graded numbers of living bacteria showed blastogenic responsiveness to Legionella preparations generally at a higher level than spleen cells from normal animals. The heightened blastogenic response was mainly evident with spleen cells obtained from mice injected with living bacteria 2 to 3 weeks earlier. Splenocytes from mice infected with legionella less than 1 to 2 weeks or for more than 4 to 5 weeks responded generally similar to those obtained from uninjected mice, indicating that sensitization with living organisms had a relatively short duration. Spleen cell suspensions responding to the L. pneumophila antigens appeared to be mainly B-lymphocytes since cell suspensions from athymic nude mice deficient in T-cells responded as well as cells from conventional mice. Furthermore, passage of splenocytes over nylon wool columns to obtain B-cell-enriched preparations resulted in cell populations capable of responding to Legionella antigen. The cell fractions rich in T-cells were much less capable of responding to the Legionella antigens. In addition, treatment of spleen cell populations with antitheta serum plus complement failed to inhibit the blastogenic response, whereas the same spleen cell preparations treated with anti-mouse immunoglobulin serum plus complement markedly diminished blastogenic responsiveness, again consistent with the likelihood that B-lymphocytes were the major cell class responding to the Legionella preparations.

Animals↗
PubMed1984

Immunostimulation by Legionella pneumophila antigen preparations in vivo and in vitro.

Injection of Legionella pneumophila antigen, either killed vaccine or soluble sonicate thereof, resulted in an enhanced antibody response by mouse spleen cells to sheep erythrocytes as determined by the hemolytic plaque assay. Enhancement was dose dependent and reached a peak response at a concentration of 10(7) bacteria or 50 micrograms of sonicate per animal. Larger doses of antigen were less stimulatory or even depressed the antibody response. Similar enhancement of antibody formation by normal spleen cell cultures to sheep erythrocytes in vitro occurred in the presence of graded amounts of L. pneumophila vaccine or sonicate. In addition, the L. pneumophila antigen stimulated enhanced background antibody formation in vitro in the absence of sheep erythrocytes or specific antigen. It appeared likely that the immunoenhancing activity of the L. pneumophila extract may be unrelated to the presence of lipopolysaccharide since boiling the antigen preparation eliminated much of the antibody-enhancing properties of the extract. A large-molecular-weight surface component from L. pneumophila was also immunomodulatory in vitro. Immunostimulation appeared to be related to effects on macrophages since adherent spleen cell populations rich in macrophages, when derived from spleen cell suspensions incubated with L. pneumophila antigen in vitro, stimulated enhanced antibody formation by normal mouse spleen cells in coculture experiments. Further investigations concerning the mechanism of immunomodulation by L. pneumophila antigen in vivo and in vitro appear to be warranted.

Animals↗
PubMed1984

Lymphoid cell blastogenesis as an in vitro indicator of cellular immunity to Legionella pneumophila antigens.

The lymphocyte blastogenic transformation assay was adapted to study responsiveness of lymphoid cells from animals and humans to Legionella pneumophila antigens in vitro. Spleen cells from guinea pigs after active immunization with Legionella vaccine, but not from normal animals, responded by blast cell transformation when stimulated in vitro with killed Legionella whole-cell vaccine, sonic extracts thereof, or a purified somatic antigen. The response was dose dependent. Similar lymphocyte blastogenesis occurred with spleen cells from mice sensitized to Legionella by sublethal infection with the bacteria. In addition, blastogenesis occurred with peripheral blood leukocytes from human volunteers tested in vitro with whole-cell vaccine, sonic extracts, or purified somatic antigen. Maximum responsiveness generally occurred 4 to 5 days after stimulation of human peripheral blood leukocytes, but a day or two earlier with spleen cells from normal or sensitized mice. Guinea pig spleen cells generally showed peak responses at the same time as human peripheral blood leukocytes after stimulation in vitro. Blastogenic responses with purified antigen were comparable to those with the whole-cell vaccine or sonic extract. Such antigens from Legionella provide a useful material for inducing responses in vitro as a correlate of cellular immunity to these bacteria.

Animals↗
PubMed1984

Myocardial infarction and severe thromboembolic complications. As seen in an estrogen-dependent transsexual.

An estrogen-dependent genetic-male transsexual had an extensive anterior wall myocardial infarction, despite insignificant coronary artery disease, a subsequent mural thrombosis, and resultant multiple cardioarterial thromboembolic events, despite heparin therapy. With an otherwise lack of cardiac risk factors, the patient was demonstrated to have an antithrombin III deficiency that resolved when conjugated estrogen therapy was withdrawn. Although congenital, plasminogen-activator dysfunction, or heparin-induced etiologies could not be ruled out, we believe this case demonstrated an estrogen-induced-antithrombin III deficiency culminating in thrombotic diathesis. This identifies a previously unrecognized population at risk. Prophylactic and therapeutic considerations are discussed.

Adult↗
PubMed1984

[Preliminary results concerning the value of chemotherapy in the treatment of inoperable bronchial carcinoma (excluding small-cell anaplastic carcinoma)].

Inoperable non- microcellular primary bronchial carcinomas have been reputed up to now to be chemo-resistant. The introduction of Cis-platinum into a polychemotherapy protocol leads to revision of this concept. The authors report the preliminary results of a polychemotherapy protocol (including Cis-platinum, Vindesine, CCNU, Cyclophosphamide) associated, in cases of non- metastasized carcinomas, with radiotherapy to the tumour itself, the mediastinum and the supraclavicular fossae. These results confirmed the value of such chemotherapy in forms with metastases. In localised inoperable forms, conclusions could be reached only on the basis of a randomised comparative trial of chemotherapy + radiotherapy versus radiotherapy alone.

Adult↗
PubMed1983

[Chondrosarcoma of soft tissue. Apropos of a case].

This article reports a case of soft-tissue chondrosarcoma in the subcutis of the right supraspinal fossa of an 18-year-old woman who had undergone irradiation in infancy. A review of 123 published cases of extraskeletal chondrosarcoma raises the question of whether or not these tumors are really malignant in patients other than children. Their relationship with previous irradiation is also examined.

Adult↗
PubMed1983

Cellular immunity to Legionella pneumophila in guinea pigs assessed by direct and indirect migration inhibition reactions in vitro.

Spleen cell cultures from guinea pigs given legionella pneumophila vaccine in complete Freund adjuvant or as a sublethal infection were inhibited in their migration activity in vitro when incubated with specific antigen. Both direct and indirect migration inhibition assays revealed sensitization of the guinea pigs to the bacterium, with demonstrable reactivity 25 to 40 days or more after sensitization. No consistent reactions occurred when the guinea pigs were given the killed Legionella vaccine in incomplete Freund adjuvant in saline. However, spleen cells from guinea pigs injected with sublethal doses of the Legionella vaccine 3 to 4 weeks earlier showed positive migration inhibition factor reactivity. Cutaneous hypersensitivity and lymphocyte blastogenic responsiveness in vitro also developed in guinea pigs sensitized with killed Legionella vaccine in complete adjuvant or given a sublethal infection with the bacterium. These results indicate that in vitro assays for migration inhibitory activity may be utilized to monitor the development of the sensitization of guinea pigs to L. pneumophila, and such reactions correlate with skin reactivity and in vitro lymphocyte blastogenic responses.

Animals↗
PubMed1983

Agar microdroplet assay for delayed hypersensitivity to Legionella pneumophila serogroup 1.

An agarose microdroplet technique was utilized to assess the cellular immunity of guinea pig lymphoid cells to Legionella pneumophila antigen in vitro. Both direct and indirect migration inhibition procedures were shown to be capable of detecting sensitization of guinea pigs to L. pneumophila antigens. Animals injected with adjuvant alone or unrelated antigens did not yield spleen cells responsive to L. pneumophila, indicating the specificity of the response. Migration inhibition factor induction by Legionella antigen in vitro correlated well with skin test responses in vivo. The positive reaction detected by migration inhibition occurred at times similar to that of skin reactivity but later than that of the earliest serum antibody titers. The assay appears to be useful for monitoring sensitization to Legionella and may be applicable to the study of cell-mediated immunity to this bacterium in infected individuals.

Animals↗
PubMed1983

Blastogenic responsiveness of spleen cells from guinea pigs sensitized to Legionella pneumophila antigens.

An in vitro leukocyte blastogenic assay was utilized to establish an in vitro correlate of cell-mediated immunity to Legionella pneumophila antigen with spleen cells from sensitized guinea pigs. Incubation of spleen cells from sensitized but not normal guinea pigs with graded amounts of killed whole cell Legionella bacteria or sonicate derived from the bacteria resulted in an antigen-induced blast cell proliferation as evidenced by an increased uptake of [3H]-thymidine into spleen cell cultures. Peak responses occurred approximately 4-6 days after incubation of the spleen cells with antigen. Sensitivity of spleen cells from animals immunized with Legionella vaccine in adjuvant persisted for at least 150 days, while responses after infection of guinea pigs with viable bacteria persisted about 4-6 weeks. The blastogenic responses of the spleen cells to Legionella antigen appeared to be a correlate of cell-mediated immunity.

Animals↗
PubMed1983

Legionella pneumophila-induced immunostimulation and blastogenesis of normal mouse spleen cells in vitro.

Cell-free sonic extracts prepared from Legionella pneumophila serogroup 1 were found to enhance the uptake of [3H]thymidine by normal mouse spleen cell cultures in vitro and also stimulate an enhanced antibody response to sheep erythrocytes, both in immunized and nonimmunized cultures. Increased background antibody responses to other erythrocyte species also occurred, indicating that the Legionella antigen was a polyclonal B cell activator. A purified cell wall component with physicochemical properties relatively similar to endotoxin, but without toxicity for mice, was found to have mitogenic activity for normal mouse spleen cells and immunostimulatory properties for anti-erythrocyte antibody response. Heating the sonicate or the purified somatic antigen for 10 min diminished immunoenhancing activity but had little effect on mitogenic properties. These results point to the complex effects of Legionella-derived antigens on normal lymphoid cell function and indicate that antigens derived from Legionella have marked immunomodulatory properties.

Animals↗