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Biomedical subjects

B Klein

Publications and source records attributed to B Klein.

At least 307 records · Page 17Linked to original sources
PubMed1985

Hematological toxicity: experience with anthracyclines and anthracenes.

Documented is hemopoietic toxicity encountered in patients with primary liver cancer (PLC), metastatic breast cancer, and colorectal cancer treated with various anthracyclines (doxorubicin [adriamycin, ADR], 4-'epidoxorubicin [4-'epiADR], and esorubicin) or anthracenes (mitoxantrone and bisantrene, as single agents as well as different combinations). Mitoxantrone, 14 mg/m2 three times weekly, was significantly more toxic than ADR, 60 mg/m2 three times weekly, for patients with PLC (P less than 0.01). In patients with colon cancer the toxicity of esorubicin did not differ significantly from that of 4-'epiADR. There was a tendency toward cumulative leukopenia with mitoxantrone and esorubicin, and cumulative thrombocytopenia with mitoxantrone and ADR. Although nadir counts for cycles 1 and 3 were similar, the percentage of patients receiving the full planned dose by the third cycle differed with the different drugs and in the different disease categories. Doxorubicin can be effectively combined with other cytostatics (e.g., cyclophosphamide + ADR + fluorouracil) to give improved results without undue hemopoietic toxicity in patients with breast cancer.

Anthracenes↗
PubMed1985

Control of human T-colony formation by interleukin-2.

T-colony formation can be induced in PHA-stimulated peripheral blood mononuclear cells (PBM) from man, but not in PHA-stimulated purified T cells, the latter requiring the presence of factors produced by PHA-stimulated PBM and termed T-colony promoting activity (TCPA). In this paper, we demonstrate that interleukin-2 (IL-2), the growth hormone of T lymphocytes, controls T-colony formation. We show that: IL-2 activity and TCPA produced by PHA-activated PBM are co-purified by gel filtration and chromatography on blue agarose, a procedure which yields a 850-fold IL-2 purification; recombinant IL-2, produced by genetically manipulated Escherichia coli, can induce T-colony formation in PHA-stimulated purified T cells; Monoclonal antibody against the IL-2 receptor (anti-Tac antibody) completely inhibits the T-colony formation in PHA-stimulated PBM when directly added to the culture system.

Antibodies, Monoclonal↗
PubMed1985

Interleukin 2 production in B cell chronic lymphocytic leukemia.

Interleukin 2 (IL 2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was investigated in 22 patients with active untreated B cell chronic lymphocytic leukemia (B-CLL) and in 15 healthy donors. PBMCs from healthy donors demonstrated an IL 2 synthesis of 12.4 +/- 10 U/mL. B-CLL PBMCs produced a significant amount of IL 2 (8 +/- 6.6 U/mL) despite the low percentage of T cells (13% +/- 8%) associated with this disease compared with that found in healthy donors (63% +/- 7.5%). If IL 2 production is expressed as units per milliliter per 10(4) T cells, its level in patients with B-CLL (1.1 U/mL/10(4) T cells) is five times greater than that of the controls (0.19 units). When expressed as units per milliliter per liter of blood, the B-CLL patients produce approximately 12 times as much IL 2 as controls. IL 2 production in normal controls was doubled after irradiation of PBMCs or addition of indomethacin. This increase was not seen with B-CLL PBMCs suggesting that the latter have been devoid of prostaglandin-producing normal IL 2 suppressor cells. By mixing normal or B-CLL T cells with non-T cells we found that T cells from patients with B-CLL stimulated by normal accessory cells produced the same amount of IL 2 as normal T cells. Moreover, B-CLL non-T cells (mainly B leukemic cells) produced no IL 2 themselves but played a much more efficient role in IL 2 production than did non-T cells from healthy donors. This was not due to detectable IL 1 production by these cells. The IL 2 produced by B-CLL PBMCs was partially purified and recovered in a 16,000 mol wt fraction, the same mol wt as IL 2 from normal cells.

Aged↗
PubMed1984

Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution.

We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1-3 (n = 8) and stage 4 (n = 5). The patients in coma stages 1-3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[Blood vessel wall regeneration in the use of a new monofilament, resorbable suture material for arterial anastomoses].

A new synthetic, absorbable suture has been tested on 15 mongrel dogs. A total of 132 simple end-to-end anastomoses has been performed in common carotid, iliac and femoral arteries and the aorta abdominalis with monofilament, absorbable polydioxanon. Aneurysms or infections did not occur. The patency rate up to 250 days was 98.5%. All vessels were studied by angiography and light- or electron-microscopy. The new monofilament suture material is characterized by extended absorption time and low foreign body reaction. It leads more rapidly to the restitution of the vascular wall than nonabsorbable sutures.

Arteries↗
PubMed1984

Human autologous rosettes. IV. Their relation with interleukin 2 activity production and natural killer cells in cancer patients.

Peripheral blood lymphocytes (PBL) of solid-tumor-bearing cancer patients produced a lower interleukin 2 (IL-2) activity after lectin stimulation than did those from normal subjects. Moreover natural killer (NK) cell activity and autologous rosette forming (ARF) cell rate are found significantly correlated with IL-2 production in these patients. No direct relation is observed between ARF cell ratio and NK cell activity in a given patient. A central role for IL-2 in cancer patient immune dysfunctions is suggested. Two lines of pathogenetic mechanisms are documented. First, PBL exhibited cellular function defects, namely, autologous receptor expression, IL-2 production, and NK activity. Second, these dysfunctions involved, at least partly, plasma factors. The possibility of specific deficiency, (e.g., thymic factors) is not documented. Conversely it is demonstrated that patient plasma contain immunosuppressive factor(s) that block(s) IL-2 production and ARF cell expression. Involvement of ARF cell receptor in T-cell activation is discussed.

Adult↗
PubMed1984

Increased sensitivity of IL2-dependent cultured T cells and enhancement of in vitro IL2 production by human lymphocytes treated with Bestatin.

Bestatin is an inhibitor of leucine aminopeptidase and aminopeptidase B which potentiates various immune functions, such as delayed hypersensitivity and antibody formation, and inhibits tumor cell growth in animal models. Our study focuses on the effect of Bestatin on interleukin 2 (IL2) sensitivity of IL2-dependent cultured T cells (CTC) and on IL2 production by human peripheral blood mononuclear cells (PBM). Bestatin (0.01 - 10 micrograms/ml) increases CTC 3H-TdR incorporation in the presence of suboptimal (low) concentrations of exogenous IL2. Bestatin alone has no mitogenic effect on CTC. This phenomenon is due to increased CTC IL2-receptors after treatment with Bestatin. Bestatin (1 - 10 micrograms/ml) also increases (1.4 - 21 fold) IL2 production by PHA-stimulated PBM. Bestatin therefore increases both IL2 sensitivity and IL2 production. This may explain the various immunopotentiating effects of Bestatin previously described.

Adjuvants, Immunologic↗
PubMed1984

Concanavalin A-induced interferon gamma production by murine spleen cells and T cell lines. Lack of correlation with Lyt 1,2 phenotype.

Concanavalin A(Con A)-induced interferon-gamma (IFN gamma) production by resting or preactivated murine spleen cells negatively selected with monoclonal antibodies specific for Lyt 1,2 antigens plus complement (C) and by interleukin 2(IL-2)-dependent T cell lines of different Lyt phenotype was studied. The data show that most of the IFN-gamma produced upon stimulation of resting spleen cells was a product of Lyt 1+2+ cells. Lyt 1-2+ cells were negative for IFN gamma production. When spleen cells that had been preactivated for 3 days with Con A were restimulated with Con A, Lyt 1+2+, Lyt 1+2- as well as Lyt 1-2+ cells produced IFN gamma in a relationship of approximately 5:3:1. In both cases the picture remained unaltered independently when the supernatants were harvested after 1, 3 or 5 days. Furthermore, two IL-2 dependent T cell lines were studied in regard to Con A-induced IFN gamma production. Line 1.3 was Thy 1+, Lyt 1-2+, whereas line 20.9. was Thy 1+, Lyt 1+2-. Both lines produced initially high titers of IFN gamma upon stimulation with Con A. After prolonged passage in vitro, however, they progressively lost the capacity to produce IFN gamma.

Animals↗
PubMed1984

Effect of cimetidine on granulocyte-macrophage colony formation by normal and chronic renal failure bone marrow cells.

The effect of cimetidine, an antihistaminic blocker of the H2 receptors, on the development of granulocyte-macrophage colonies (GMC) was examined in vitro on bone marrow cells from healthy individuals and chronic renal failure (CRF) patients. The drug caused a dose-dependent decrease in the number of GMC from bone marrow samples in both healthy subjects and patients, being much more expressed in the latter group. The addition of urea to bone marrow cultures of healthy subjects increased the inhibition of colony formation caused by cimetidine alone. CRF or control serum added to normal bone marrow cells enhanced the colony growth which was significantly more expressed when using a CRF serum sample.

Adult↗
PubMed1984

Transfection with extracellularly UV-damaged DNA induces human and rat cells to express a mutator phenotype towards parvovirus H-1.

Human and rat cells transfected with UV-irradiated linear double-stranded DNA from calf thymus displayed a mutator activity. This phenotype was identified by growing a lytic thermosensitive single-stranded DNA virus (parvovirus H-1) in those cells and determining viral reversion frequencies. Likewise, exogenous UV-irradiated closed circular DNAs, either double-stranded (simian virus 40) or single-stranded (phi X174), enhanced the ability of recipient cells to mutate parvovirus H-1. The magnitude of mutator activity expression increased along with the number of UV lesions present in the inoculated DNA up to a saturation level. Unirradiated DNA displayed little inducing capacity, irrespective of whether it was single or double stranded. Deprivation of a functional replication origin did not impede UV-irradiated simian virus 40 DNA from providing rat and human cells with a mutator function. Our data suggest that in mammalian cells a trans-acting mutagenic signal might be generated from UV-irradiated DNA without the necessity for damaged DNA to replicate.

Animals↗
PubMed1984

Generation of superoxide anions during phagocytosis by monocytes of uremic patients.

The phagocytic activity of monocytes from 15 uremic patients was estimated by the superoxide anion test. There was a significant decrease in the ability of monocytes from these patients to produce superoxide anions in comparison with monocytes obtained from healthy subjects. Addition of urea to monocytes from healthy subjects caused a marked reduction in their ability to produce superoxide anions, while addition of creatinine did not cause any effect. Monocytes from patients with renal failure of glomerular origin were found to produce less superoxide anions than those from patients with other types of renal diseases.

Creatinine↗
PubMed1984

Phage-types and susceptibility to 26 antibiotics of nosocomial strains of Acinetobacter isolated in Portugal.

Sixty-two strains of Acinetobacter calcoaceticus isolated from pathological samples or from the environment in several hospitals in Lisbon, were studied by means of two complementary phage-typing systems. Eighteen phage-types or sub-types, one group of uncommon types (9.6%) and one group of untypable strains (20.9%) were found. A new phage-type (No. 104) and a new sub-type (No. 18) were defined among the Portuguese strains. The in vitro activity of 26 antibiotics against 48 nosocomial strains was studied by the Kirby-Bauer method. The most active antibiotics were, in decreasing order, amikacin, carbenicillin, tobramycin, minocycline, dibekacin, doxycycline, sisomycin, trimethoprim-sulphamethoxacole, ticarcillin and piperacillin. The strains were also tested against 4 new beta-lactam antibiotics, and the MICs were determined by an agar dilution method. N-formimidoyl-thienamycin was found to be the most active against Acinetobacter and ceftazidime was considerably more active than apalcillin and cefotaxime.

Acinetobacter↗
PubMed1984

The role of interleukin-2 in T colony formation by human pre-T cells (pTCFC).

Human T lymphocyte colonies may be grown in agar from pre-T peripheral blood cells. Pre-T cells giving rise to these colonies represent 0.5% of the non-adherent, E rosette and Leu 1 depleted mononuclear cell subpopulation. T colony formation is induced by PHA stimulation and only if media conditioned by PHA stimulated peripheral blood lymphocytes (PHA-LCM) is added. These media contained interleukin-2 (IL-2) and T colony promoting activity (TCPA) for pre-T cells. TCPA is co-eluted with IL-2 by gel filtration with an apparent molecular weight of 18,000 daltons. Moreover, when PHA-LCM are absorbed on IL-2-dependent cultured T cells, TCPA is removed as well as IL-2. In attempt to further demonstrate the role of IL-2 in T colony formation by the pre-T cells we used the anti-Tac monoclonal antibody directed against IL-2 receptor. We demonstrated that anti-Tac inhibits T colony formation in a dose-dependent manner in pre-T cells. We conclude that IL-2 is the essential exogenous factor contained in PHA-LCM which allows pre-T cell differentiation expression and proliferation in agar medium.

Antigens, Surface↗
PubMed1984

Low dose of deoxyguanosine increases IL-2 receptors of IL-2-dependent cultured T cells.

Deoxyguanosine ( dGuo ) is a purine nucleoside phosphorylase (PNP) substrate which has been shown to inhibit T lymphoblast growth, PHA-induced cell proliferation and suppressor T cell activity. Low dGuo concentrations (0.5-5 microM) increase interleukin-2 (IL-2) sensitivity of IL-2-dependent cultured T cells (CTC). dGuo alone has no direct mitogenic effect on CTC. The increased IL-2 sensitivity of CTC was more marked in the presence of low IL-2 concentrations than high ones. CTC incubated with dGuo at 37 degrees C for 24 hrs absorbed more exogenous IL-2 than control non-treated CTC. CTC incubated at 4 degrees in the presence of dGuo did not absorb any more IL-2 than control CTC. FACS analysis further showed increased Tac expression on CTC due to dGuo . These findings indicate that a 37 degrees incubation of CTC with dGuo increases the number of CTC IL-2 receptors. dGuo was not found to increase IL-2 production by PHA-stimulated PBM. Therefore, low dGuo concentrations selectively augment the sensitivity of cells responding to IL-2 by increasing IL-2 receptors.

Cells, Cultured↗
PubMed1983

The role of interleukin 1 and interleukin 2 in human T colony formation.

We investigated the roles of interleukin 1 (IL1) and interleukin 2 (IL2) on T colony formation by PHA-stimulated peripheral blood lymphocytes (PBL). Purified T cells stimulated by PHA could not generate T colonies as did PBL. Media conditioned by PHA-stimulated PBL (PHA-LCM) contained IL2 and a T colony-promoting activity (TCPA) which induced T colony formation in PHA-stimulated purified T cells. IL2 and TCPA are coeluted in the same peak of 18,000 molecular weight after gel filtration chromatography. Moreover, TCPA present in the PHA-LCM could be absorbed on IL2-sensitive cells which possessed specific receptors for IL2. These results suggest that TCPA and IL2 are related entities. Monocytes or IL1 (a monokine released by activated monocytes) also induced T colony formation in purified T cells. Phorbol myristate acetate (PMA) could replace monocytes in the induction of T colony. Monocytes, IL1, or PMA are known to be crucial requirements for IL2 production by PHA-stimulated T cells. This combined with the fact that IL2 participates in T colony formation suggests that monocytes induce T colony formation through IL2 production.

Clone Cells↗
PubMed1983

Microinjection of human cell extracts corrects xeroderma pigmentosum defect.

Cultured fibroblasts of patients with the DNA repair syndrome xeroderma pigmentosum (XP) were injected with crude cell extracts from various human cells. Injected fibroblasts were then assayed for unscheduled DNA synthesis (UDS) to see whether the injected extract could complement their deficiency in the removal of u.v.-induced thymidine dimers from their DNA. Microinjection of extracts from repair-proficient cells (such as HeLa, placenta) and from cells belonging to XP complementation group C resulted in a temporary correction of the DNA repair defect in XP-A cells but not in cells from complementation groups C, D or F. Extracts prepared from XP-A cells were unable to correct the XP-A repair defect. The UDS of phenotypically corrected XP-A cells is u.v.-specific and can reach the level of normal cells. The XP-A correcting factor was found to be sensitive to the action of proteinase K, suggesting that it is a protein. It is present in normal cells in high amounts, it is stable on storage and can still be detected in the injected cells 8 h after injection. The microinjection assay described in this paper provides a useful tool for the purification of the XP-A (and possibly other) factor(s) involved in DNA repair.

Cell Extracts↗
PubMed1983

Myeloproliferative sarcoma virus: its effects on erythropoiesis in adult DBA/2J mice.

Adult susceptible mice (DBA/2J) infected with MPSV (myeloproliferative sarcoma virus), a defective RNA tumour virus, develop splenomegaly and progressive disruption of the haematologic system culminating in death. The present study was specifically directed toward determining the effects of the virus on erythroid differentiation. Early and late precursor cells (erythroid burst-forming units; BFU-E and colony-forming units; CFU-E, respectively) were evaluated by the ability of bone marrow and spleen cells to form colonies of fully differentiated erythroid cells in vitro. MPSV caused substantial modification of both the BFU-E and CFU-E populations in the bone marrow and spleen of infected animals. Changes were detected in the CFU-E population preceding any significant increase in spleen weight. In the bone marrow, the proportion of CFU-E cells increased almost twofold by days 5-10 after virus infection but decreased by day 15. In the spleen, CFU-E frequency rose 40-fold by days 10-15 and then declined steadily prior to death. At the peak of CFU-E expansion, a small proportion of the population appeared to be erythropoietin (Ep) independent, although there was no evidence of a complete switch to Ep-independence which occurs in Friend virus-induced erythroleukemia. Dose-response curves showed that none of these data could be explained in terms of a changing responsiveness to Ep. However, evidence is presented that indicates that BFU-E from MPSV-infected animals lose or have a reduced requirement for burst-promoting activity (BPA) relative to normal cells although their progeny still need Ep for terminal erythroid differentiation.

Animals↗