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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 721 records · Page 40Linked to original sources
PubMed1984

Whole body oxygenation using intraperitoneal perfusion of fluorocarbons.

A preliminary study was undertaken to assess the feasibility of increasing the arterial oxygen tension, and decreasing the arterial carbon dioxide tension, in intact animals, by means of peritoneal perfusion with the perfluorocarbon-containing, oxygen-transporting blood substitute, 20% Fluosol-DA. Perfusion was carried out in rabbits using a bubble oxygenator and circulator pump, delivering Fluosol at a rate of 25 ml min-1. Control blood-gas measurements were carried out at various FIO2 between 0.5 and (if the animal was not severely hypoxic) 0.16. The measurements were repeated during the intraperitoneal perfusion of Fluosol. At all values of FIO2, significant increases in PaO2 were seen (P less than 0.05). Significant decreases of PaCO2 (P less than 0.05) were seen if the animals were not hypoxic (PaO2 greater than 10 kPa).

Animals↗
PubMed1984

Composition of a suppressor factor that inhibits the immune response to lactate dehydrogenase B.

Hybridomas obtained by fusion of lactate dehydrogenase B (LDHB)-activated suppressor T (Ts) cells with the BW5147 thymoma produce a suppressor factor (TsF) that inhibits the proliferation of LDHB-activated helper T (Th) cells. A similar factor (TsE) is contained in the extract of suppressor hybridomas. Both TsF and TsE are specifically retained by LDHB-immunoadsorbent columns. Both consist of two components, an antigen-binding component (ABC) and possibly a major histocompatibility complex (MHC) component. The latter reacts with certain monoclonal antibodies specific for MHC determinants. The two components are covalently associated in the TsF and noncovalently associated in TsE. Mixing of the two components reconstitutes the activity of the TsF or TsE. Disruption of the ABC's tertiary structure results in its inability to reconstitute suppressive activity on mixing with the MHC components. The ABC may contain an intrachain disulphide bond(s). Suppression is obtained when Th cells are incubated first with the ABC and then with the MHC component or vice versa, provided that the incubation period is at least 4 h. The MHC component is also produced by nonsuppressor hybridomas but not by mitogen-stimulated blasts or by the parental thymoma. The TsF is a glycoprotein with a molecular weight of about 120,000 to 160,000. The molecular weight of the ABC is about 76,000-86,000 and of the MHC component about 30,000-37,000.

Animals↗
PubMed1984

Pharmacokinetics of fentanyl in children with renal disease.

Two cases of fentanyl anesthesia in children with renal diseases are described. In a case of end stage renal failure, the pharmacokinetic parameters during cardiac surgery were similar to 18 children from the same age group with normal renal function. In a case of Wilm's tumor, there was an unusually prolonged elimination half-life of fentanyl and smaller distribution volume as compared to pediatric parameters during fentanyl anesthesia.

Anesthesia, Intravenous↗
PubMed1984

Class I restricted interaction between suppressor and cytolytic cells in the response to minor histocompatibility antigens.

Inoculation of 10(8) unirradiated, minor H antigen-incompatible spleen cells into recipients leads to a failure of the induction of cytolytic T lymphocytes (CTL) specific for these antigens. In contrast, a strong CTL response against minor H antigens is obtained when the inoculated cells are irradiated or treated with Thy-1-, Lyt-1- or Lyt-2-specific antibody and complement. Thus the failure of CTL induction is probably due to suppression mediated by radiosensitive, Lyt-1+2+ T cells in the immunizing inoculum. We demonstrate here that the inoculated cells must share class I MHC loci with the recipients for the suppression to occur. Thus, the interaction between the suppressor T (Ts) cells and their targets (presumably the CTL precursors) is restricted by class I molecules. A disparity at class II loci between the inoculated cells and the recipients overrides the class I-restricted suppression, possibly through a positive allogeneic effect. The simplest interpretation of the class I restriction of Ts cell-target cell interaction is that the CTL precursors recognize minor H antigens in the context of class I molecules on the surface of the Ts cells themselves.

Animals↗
PubMed1984

Qa-like genes defined by CTL analysis of B10.W lines.

Twelve responder-stimulator combinations of mouse B10.W strains identical at K, D, and class II loci were tested for the generation of cytolytic T lymphocytes (CTL). No primary CTL could be obtained in any of the combinations but in nine combinations CTL were generated after priming in vivo. Six of these CTL are described. They define five antigenic determinants expressed exclusively in a small group of B10.W lines. The determinants appear to be part of the same system that resembles the Qa system originally defined in classic inbred strains. This resemblance rests on the observation that in vivo priming is necessary for the generation of the CTL, and that the CTL are not restricted in their reactivity by known H-2 loci. At least some of the determinants, however, appear to be controlled by a locus (or loci) associated with the K-rather than the D-end of the H-2 complex. Furthermore, some of the CTL directed against these Qa-like determinants cross-react with a molecule controlled by the K locus.

Animals↗
PubMed1984

The role of T cell subsets in the generation of secondary cytolytic responses in vitro against class I and class II major histocompatibility complex antigens.

Strain combinations generating cytotoxic T lymphocytes (CTL) specific for a single class I (K or D) or class II (A or E) MHC molecule were set up. The responder cells were separated into Ly subsets (Ly-1+2-, Ly-1-2+, and Ly-1+2+) on day 5 of culture by using lytic or non-lytic selection techniques and monoclonal Ly-specific antibodies. The separated subsets were restimulated on day 8 and tested for secondary CTL activity on day 12. Class II-specific secondary CTL could be generated from all three subsets, whereas class I-specific CTL developed only in the Ly-1+2+ and Ly-1-2+ subsets. The Ly-1+2+ cells underwent a phenotypic shift to Ly-1-2+ by day 12, whereas CTL generated from the Ly-1+2- and Ly-1-2+ subsets retained their phenotype up to the secondary effector stage. The cells separated according to their Ly phenotypes on day 5 were the progeny of unprimed progenitors expressing the same Ly phenotypes. Unprimed Ly-1+2+ cells gave rise to CTL in the absence of the other subsets, while unprimed Ly-1+2- and Ly-1-2+ cells required the help of Ly-1+2+ cells (or soluble factors) during priming to become non-lytic CTL precursors by day 5, and cytolytic cells after restimulation. The Ly-1+2- subset could generate class II-specific secondary CTL only in the absence of the other two subsets. Apparently, alloantigen-primed Ly-1+2+ and Ly-1-2+ cells suppressed the development of cytolytic activity in the Ly-1+2- subset. The combined data provide a comprehensive pathway of CTL differentiation from T cell subsets.

Animals↗
PubMed1984

Mechanisms involved in the Ir-gene control of T suppressor cell response to lactate dehydrogenase B.

It has now been widely accepted that the immune response (Ir)-gene control of T helper (Th)-cell responses reflects the influence of class II major histo-compatibility complex (MHc) molecules on T-cell specificity. This influence can either be exerted during T-cell ontogeny and result in class II allele-dependent differences in the T-cell repertoire, or manifests itself during the immune response as a restricted capacity of class II molecules to associate with foreign antigens in a form recognizable by Th cells. Depending on the level at which class II Mhc molecules act, the cause of nonresponsiveness to certain antigens can be either the absence of the relevant clones from the T-cell repertoire (as a result of Mhc-dependent positive or negative selection mechanisms), or the incapability of a particular class II molecule to form a complex with a foreign antigen on the surface of antigen presenting cells (APC). It is well known that T suppressor (Ts)-cell responses can also be under Ir-gene control, as reflected in the Mhc-dependence of Ts cell-generation in response to certain antigens. However, the mechanisms involved in this Ir-gene control are less well understood. We have used here the immune response to lactate dehydrogenase B (LDHB) as a model to explore the mechanisms causing absence of suppression ("Ts-cell nonresponsiveness"). The LDHB system is suitable to investigate this question, because the LDHB-specific Ts cells are Mhc-restricted, and only two allelic forms, b and k, of the E beta class II polypeptide can serve as restriction elements for Ts-cell generation; mouse strains not expressing these molecules are Ts-cell nonresponders. We applied here the methods previously used to analyse nonresponsiveness of Th cells to the Ts-cell response. The approach was to generate LDHB-specific Ts cells in vitro, by presenting the antigen on Mhc-disparate APC (allorestricted Ts cells). The results have demonstrated that Ts cells from two representative Ts-responder strains can be generated in the context of several but not all allogeneic E molecules. The non-responsiveness observed in certain allogeneic T cell-APC combinations could not be explained by defective antigen presentation. Thus, these cases of Ts-cell nonresponsiveness, similar to Th-cell nonresponsiveness, might have resulted from the absence of the relevant T-cell clones from the repertoire of the strain tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

H-41, a new minor histocompatibility locus. I. Histogenetic analysis.

The B10.STA12 mouse congenic line inherited from the wild mouse parent not only the H-2w13 haplotype but also an allele at a minor H locus, which we designate H-41. This allele (H-41a) differentiates the B10.STA12 line from B10.STA10 and B10.LIB55, which carry identical H-2w13 haplotypes but a different H-41 allele (the H-41b, also present in the background strain C57BL/10Sn). The B10.STA12 and B10.STA10 lines reject each other's skin grafts and generate cytolytic T lymphocytes (CTL) after in vivo immunization and in vitro restimulation with cells of the partner strain. The B10.STA12 anti-B10.STA10 CTL react with B10.STA10, B10.LIB55, and B10.STA39 target cells and with cells of F1 hybrids between the responder strain B10.STA12 and strains C57BL/6, C57BL/10, C57L, BALB/c, A, AKR, WB, DBA/1, and DBA/2 but fail to react with (C3H x B10.STA12) F1 and (CBA x B10.STA12) F1 cells. The B10.STA10 anti-B10.STA12 CTL react with B10.STA12, B10.P, and C3H.NB cells but fail to react to (B6 x B10.STA10) F1 target cells. The CTL reactivity in both combinations is Dp restricted. The B10.STA10 anti-B10.STA12 CTL exhibit, in addition, a cross-reactivity with B10.SAA48 cells that may be directed at one of the alloantigens controlled by the H-2 haplotype of this strain.

Animals↗
PubMed1984

Manipulation of anti-LDH-B response by T suppressor factors.

Hybridomas produced by fusion between the BW5147 thymoma and an LDH-B-specific B10.A(2R) suppressor T cell line secrete two T suppressor factors (TsF). One factor (TsF-A) shares Mhc determinants with the A alpha A beta molecule and suppresses proliferating Th cells; the other (TsF-E) shares determinants with the E alpha E beta molecule and it inhibits the maturation of the T suppressor (Ts) cells. Here we demonstrate that the two factors can be used to alter the immune response status of cultured T lymphocytes or of an animal. When added to a culture of LDH-B-primed cells or injected into mice, the TsF-A turns responders into nonresponders, presumably by blocking the proliferation of the Th cells. The TsF-E converts nonresponder cultures or mice into responders, presumably by preventing the differentiation of Ts cells. As there are good prospects for obtaining TsF in large quantities and in a highly purified form, this manipulation of the immune response by the deployment of specific factors promises to become an efficient new method of immunotherapy.

Animals↗
PubMed1984

Pediatric fentanyl dosing based on pharmacokinetics during cardiac surgery.

The pharmacokinetics of fentanyl (F) were studied in 10 children, age 5 months-4.5 yr (mean 19 months) undergoing cardiac surgery with cardiopulmonary bypass ( CPBP ). They suffered from transposition of the great arteries (6), tetralogy of Fallot (2), and atrio-ventricular (A-V) canal (2). Induction of anesthesia included a bolus of 50 micrograms X kg-1 X min-1 F followed by a continuous F infusion of either 0.15 micrograms X kg-1 X min-1 (4 patients) or 0.3 micrograms X kg-1 X min-1 (6 patients). The F infusion was discontinued when cardiopulmonary bypass was started, 81-141 min (mean 112 min) along with deep hypothermia. Blood was collected throughout surgery from an indwelling radial arterial catheter and plasma concentration of F was assayed by GLC. F plasma concentrations after 30 min were 2-3-fold higher than reported with the same regimen in adults. The calculated values for t1/2 alpha (12 +/- 9 min) (mean +/- SD), t1/2 beta (141 +/- 98 min) and total body clearance (12.8 +/- 7.3 ml X min-1 X kg-1) were similar to adult values. The significantly lower steady-state volume of distribution observed in children with intracardiac shunts (1385 +/- 875 ml X kg-1) compared to reported values for adults (3200-6000 ml X kg-1) explains the higher F plasma concentrations achieved in these children. Cardiopulmonary bypass produced a mean 70% (range, 56-89%) decrease in plasma F, significantly higher than would be expected from hemodilution alone. Studies of F disposition in the CPBP demonstrated that F is bound to the pump.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗
PubMed1983

Monoclonal suppressor factor specific for lactate dehydrogenase B. I. Mechanism of interaction between the factor and its target cells.

Hybridomas secreting a monoclonal T suppressor-effector factor (TseF) were produced by fusion of a lactate dehydrogenase B (LDHB)-specific long-term T suppressor-effector (Tse) cell line with the BW5147 thymoma. A short exposure (4 h) to TseF completely suppresses the antigen-specific and A-restricted proliferation of LDHB-primed Lyt-1+2- [possibly helper (Th)] cells. The action of TseF on Th cells, as that of the Tse cells themselves, is antigen-specific and A-restricted. The interaction of TseF with Th cells involves two binding events, of which one occurs via antigen bridge, and the other represents the recognition of a factor-derived Ak-like moiety by the anti-Ak receptor of Th cells. The Ak-like moiety of the TseF carries the determinants that serve as restriction elements for antigen recognition by Th cells, and additional determinants demonstrable by T cell-specific monoclonal "anti-Ak" antibodies, however, it lacks serologically detectable determinants of the B cell-derived A alpha A beta class II Mhc molecules.

Animals↗