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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 469 records · Page 26Linked to original sources

Defective cytotoxic T-cell generation in Moloney murine sarcoma virus-infected A/Sn mice.

Cytotoxic T-cells (CTL) could not be detected in spleen cell suspensions from Moloney murine sarcoma virus (M-MuSV)-induced tumor-bearing A/Sn and (A/Sn X C57BL/6) F1 mice, with the A/Sn-derived natural killer (NK)-sensitive YAC-1 lymphoma cells used as targets. However, spleen T-cells from tumor-bearing (A/Sn X C57Bl/6)F1 mice were efficient killers against C57BL/6-derived RBL-5 cells. When tested for viral antigens by sera from mice with regressing atumors, YAC-1 and RBL-5 cells cross-reacted. The anti-RBL-5 effect of spleen cells from A/Sn X C57BL/6)F1 tumor bearers was blocked in cold target competition experiments by YAC-1 cells, which suggested the expression of a CTL target structure on YAC-1 cells. The activity against YAC-1 cells in spleen suspensions of both tumor-bearing and control (A/Sn X C57BL/6)F1 mice seemed to be an NK phenomenon entirely, because blocking occurred neither with RBL-5 cells nor with freshly prepared YAC lymphoma cells, both of which have low sensitivity to NK effects. Spleen cells from (A/Sn X C57BL/6)F1 regressors were stimulated to a secondary CTL response in vitro by YAC-1 and RBL-5 cells, which further indicated that YAC-1 cells express the M-MuSV-specific CTL target structure. These experiments also showed that YAC-1 cells could be lysed by CTL. YAC-1 cells did not induce a secondary response in A/Sn regressors, which indicated a lack of M-MuSV-induced CTL memory cells in this strain. The result was not due to a general unreactivity of A/Sn mice against YAC-1 cells, because spleen cells from YAC-1-immunized mice exhibited strong T-cell-mediated anti-YAC-1 activity after in vitro cultivation. Thus tumor regression seems to occur without the production of CTL in A/Sn mice.

Animals↗

Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs.

Pancreatic excretion of ampicillin was evaluated in normal dogs and in dogs with induced pancreatis. A 100-mg/kg ampicillin dose administered intravenously induced mean peak serum levels of 100 micrograms/ml, and a 200-mg/kg intravenous dose induced a mean peak serum level of 273 microgram/ml. Ampicillin serum levels did not differ between the group of normal dogs and those with pancreatitis. In normal dogs, the peak pancreatic fluid ampicillin concentration after the 100-mg/kg dose was 0.4 microgram/ml, and that after the 200-mg/kg dose was 2.7 micrograms/ml. In dogs with pancreatitis, the mean peak ampicillin concentration in the pancreatic fluid after the 100 mg/kg dose was 19 micrograms/ml, and that after the 200-mg/kg dose was 38.5 micrograms/ml. Pancreatic fluid ampicillin concentrations were therapeutic in dogs with pancreatitis and subtherapeutic in normal dogs.

Ampicillin↗

Lymphotoxins: selective cytotoxic effects.

Materials with lymphotoxin activity produced by lectin stimulated primary cultures of human lymphocytes enriched for T cells or B cells, as well as material obtained from established tissue culture lines of human lymphoid cells were tested for cytotoxicity towards a large number of primary cultures and established lines of human and animal cells. Highly selective effects were found. The patterns of responses to the various lymphotoxin preparations indicate heterogeneity not only among the different cell cultures but also among the lymphotoxin preparations. In addition to the heterogeneity of the various cell cultures in their responses to the lymphotoxin preparations, a spectrum of susceptibilities was also noted among clonal derivatives of the same parental lines. In quantitative terms the responses of the most resistant and the most susceptible cell cultures spanned approximately a 200-fold range. These findings could have bearing upon the mechanism of tumor evasion of host antitumor immunity.

Animals↗

Blood lymphocytes in infectious mononucleosis share the following characteristics with activated T cells: natural attachment, stable E rosetting and glucocorticoid sensitivity.

Blood lymphocytes of infectious mononucleosis (IM) patients, unlike these obtained from healthy individuals, exhibit the following characteristics of activated T cells: (1) "stable" E rosette formation; (2) natural attachment to various human normal and malignant cells; (3) sensitivity in vitro to the lytic effect of glucocorticoids. Although the IM T cells attach in vitro to all the human cells tested, they kill only the EBV genome carrying targets. The possibility is discussed that some of the activated T cells in IM result from a non-specific activation elicited by the T cells responding specifically to the EBV associated antigens.

Cell Adhesion↗

Stimulation of phagocytic activity of neutrophilic granulocytes by sera of patients with solid tumors.

The effect of serum of patients with solid tumors on the phagocytic activity of normal neutrophilic granulocytes was investigated. The largest groups of tumors studied were carcinoma of colon/rectum, sarcomas and melanomas. Sera from all three groups of patients were found to have highly significant (p < 0.001) stimulatory effects on granulocyte phagocytic activity. These findings contrast with previously reported depression of granulocyte phagocytic activity associated with various forms of leukemia and lymphomas.

Clinical Trials as Topic↗

Osmotic concentration of polypeptides from hemofiltrate of uremic patients.

Hemofiltrate from uremic patients was concentrated 15- to 40-fold by osmotic removal of water across a reverse osmosis membrane which retains salts and proteins. Salts and low molecular weight components were removed from the concentrate by partial dialysis using a highly impermeable cellulose membrane. Following this desalting step, 100- to 500-fold concentration could be achieved by evaporation at low pressure. The concentrate was fractionated on Sephadex G15 columns. Fractions were tested for their toxicity to human cells in culture. Fractions containing components with molecular weights greater than 700 daltons inhibited 3H-thymidine incorporation into the DNA of HeLa and skin fibroblast cells more than did low molecular weight peptides and an iso-osmolar control. Components eluting in the molecular weight range of angiotensin I and vitamin B-12 were most inhibitory. These studies show that hemofiltrate from uremic patients is a readily available source of toxic polypeptides. The osmotic concentration and gel chromatographic procedures described should make available large amounts of these molecules for further studies.

Animals↗

Cell-surface antigens induced by RNA tumour viruses.

Host animals show an immune response to the surface of cells infected with RNA tumour viruses. An element of this response is due to expression of viral structural antigens, but the major part is due to virus-induced cell-surface antigens (CSAs). This article compares the properties of CSAs of the avian, murine and feline retrovirus systems.

Antigens, Neoplasm↗

Regulation of tumor growth and antibody clone expression by antigen and anti-idiotype antibody ligands with specificity for receptor-binding sites.

Dextran ligands, modified to increase epitope reactivity with receptors, were more effective in suppressing BALB/c mouse plasmacytomas MOPC 104 E and J-558, which bind alpha (1 leads to 3) dextran and have an idiotype (Id) in the common, than autoantibody (Ab) against the Id unique to each of the proteins secreted by the two tumors (the (IdI). BALC/c immunized with 104 E myeloma protein and expressing an antibody response to the 104 E IdI exhibited a specific, anti-104 E IdI transplantation resistance to lethal grafts of 104 E, but not J-558, tumors notwithstanding the shared common Id and similar ability to bind alpha(1 leads to 3) dextran. This autoantibody did not prevent modulation of the 104 E tumor to variant forms or the growth of the variants. On challenge with alpha (1 leads to 3) dextran, the immunized mice expressing the anti-104 C IdI responses failed to express the 104 D IdI-like antibody clone present in the normal, anti-alpha (1 leads to 3) dextran antibody repertoire. Passive, iso-anti-104 E IdI antibody had a transitory suppressive effect on the normal, 104 E IdI-like antibody clone but failed to circumvent 104 E tumor growth. It is apparent that the greater effectiveness of ligands strongly reactive in a nonphysiological manner with the tumor receptors lies in the stabilization of the tumor load without inducing variant escape or a disturbance of the immune network, and that receptor expression and malignancy state are not necessarily co-extensive functions.

Animals↗

Explorations of antimitotic agents in the treatment of a congenital disease, ichthyosis linearis circumflexa.

Successful therapy of a genetic disorder, Ichthyosis Linearis Circumflexa, was achieved using a low dose systemic cyclophosphamide. Prior to such therapy, 80 to 90% of the body surface was affected; the use of antimitotic agents reduced the extent of the lesions to less than 15% of the body surface. As a result, the clinical status was changed from severely disabling to being compatible with a normal way of life. It is believed that this phenomenon is related to selective effects of cyclophosphamide, such as those on lymphocyte subpopulations. To our knowledge, successful chemotherapy for diseases of genetic or congenital origin has not been previously reported.

Adult↗

Mutilating sclerosing basal cell epithelioma.

A 59-year-old black woman presented with an ill-defined plaque on her nose. This appeared clinically suggestive of a sclerosing type of basal cell epithelioma (BCE). Microscopic sections demonstrated this diagnosis. Multiple excisions employing the microscopically controlled technique of Mohs traced the tumor deep into the nasal cartilage before histologic sections were free of tumor cells. This type of BCE deserves well planned therapy because of its destructive potential.

Basal Cell Carcinoma↗

Neuroendocrine function in long-term pinealectomized male rats, following visual and audiogenic stress.

Intact, sham-pinealectomized and pinealectomized adult male rats were maintained for 10 weeks on a light : dark (L : D) cycle of 12 : 12,with lights on at 6 a.m. Subsequently they were acutely exposed to (1) visual or (2) audiogenic stress for periods of 2 or 30 min, immediately following which they were decapitated and serum ACTH, corticosterone, FHS, LH, PRL and TSH concentrations were determined. Serum ACTH and corticosterone levels were similar in control and operated groups following both types of stresses. Serum FSH and LH concentrations were elevated in pinealectomized animals as compared to controls, following 30 min of exposure to visual stimulation; no difference in these parameters was observed between the groups following audiogenic stress. Serum PRL levels tended to be lower in pinealectomized animals following both stresses. Serum TSH concentrations following visual stimulation were similar in all groups, but audiogenic stimulation resulted in elevated TSH levels as compared to controls. These data demonstrate that the pineal gland plays an integral role in the responses of the parvicellular neuroendocrine axes to acute neurogenic stress. Possible molecular bases for this involvement are discussed.

Acoustic Stimulation↗