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Biomedical subjects

E Leiter

Publications and source records attributed to E Leiter.

At least 37 records · Page 2Linked to original sources

Relationship of interferon-gamma and neopterin levels during stimulation with alloantigens in vivo and in vitro.

We have recently shown that interferon-gamma is capable of activating the key enzyme of pterin biosynthesis in macrophages. This leads to excretion of the stable degradation product neopterin. In this article we present experimental evidence suggesting that stimulation of T cells by alloantigens is associated with release of interferon-gamma--which, in the case of rejection, is locally restricted and not always detectable in the bloodstream. Neopterin induced by this lymphokine, however, readily penetrates tissue barriers and is detectable in the serum. This conclusion is based on two different sets of observations: (1) If supernatants of MLCs are compared with sera from patients with documented acute rejection episodes for their interferon-gamma and neopterin levels, a marked gradient is observed to exist between interferon levels measured in vitro and in vivo; this is not the case for neopterin for which comparable levels were seen. (2) Detection of interferon-gamma in sera of allograft recipients invariably precedes an increase of neopterin; on the other hand, increasing neopterin counts are also seen in the absence of detectable interferon-gamma levels in the serum. It thus appears that although interferon-gamma release during allograft rejection is primarily restricted to the tissue, evaluation of certain metabolites of interferon-dependent metabolic pathways enables definition of its endogenous release. Whereas interferon gamma represents a less reliable marker in the monitoring of rejection episodes, it might offer an additional means to differentiate rejection from systemic infections. Such a discrimination can not be achieved with the neopterin marker.

Acute Disease↗

Use of donor-specific T-cell lines for monitoring of human allograft recipients. I. Demonstration of IgG binding to autologous TCL.

Donor-specific and highly cytotoxic T-cell lines (TCL) as well as lectin-induced TCL were established from pretransplant lymphocytes of 6 cadaveric renal allograft recipients. These TCL were used in the 125I-staphylococcus protein A assay to detect IgG antibodies in pre- and posttransplant sera of these patients preferentially binding to autologous donor-specific TCL. Such antibodies were detected in pretransplant sera from 4 of these 6 allograft recipients. Antibody levels in these 4 patients and in 1 additional case who became positive after transplantation further increased during acute cellular rejection episodes. They disappeared after successful treatment but remained elevated until transplantectomy for treatment of irreversible rejection in 1 case. IgG antibodies binding to autologous lectin-induced TCL were detected in only 1 patient and exhibited a pattern clearly different from those binding to donor-reactive TCL. Although attempts to define the antigenic specificity of the autoantibodies binding to donor-specific TCL by genetical and biochemical means has remained unsuccessful so far, the demonstration of their relationship to in vivo expansion of donor-reactive immune cells deserves further attention.

Adult↗

Surface glycoproteins (S-GP) on normal and malignant human leukocytes.

This study aimed to investigate high molecular weight surface glycoprotein (S-GP) patterns on various types of human leukocytes. S-GP were externally labelled by the Galactose-oxidase-NaB3H4 technique. Results based on the analysis of 120 samples derived from different types of normal and malignant leukocytes indicate that the relative expression of high molecular weight S-GPs changes during haemopoietic cell differentiation and to some extent these changes enable the classification of human leukocytes.

Antigens, Surface↗

Evaluation of spontaneous lymphocyte proliferation by single cell autoradiography in human allograft recipients.

Spontaneous lymphocyte proliferation was studied in 22 patients receiving cadaveric renal transplants before and at various times after grafting. Prophylactic immunosuppression consisted of CyA and prednisone. Spontaneous lymphocyte proliferation was evaluated in a total of 500 single cell autoradiographs after short term in vitro incubation with [3H]TdR. In 13 patients without clinical problems a transitory increase of lymphocyte labeling indices to approximately five times the pretransplant levels was observed. The failure to detect such increments in two patients receiving optimally matched grafts suggested that this early proliferative lymphocyte peak might be caused by in vivo recognition of major histocompatibility antigens. Much higher labeling indices were detected in close temporary association with acute cellular rejection (4 cases), severe infections and withdrawal of CyA (3 cases) and venous thrombosis (1 case). Only moderately elevated numbers of spontaneously proliferating lymphocytes were seen in one patient with a reversible vascular rejection episode. It appears that assessment of spontaneous lymphocyte proliferation is capable of discriminating on a quantitative level between patients with and without clinical problems such as acute cellular rejection and infection.

Adolescent↗

Effects of human recombinant alpha 2 arg-interferon and gamma-interferon on human breast cancer cell lines: dissociation of antiproliferative activity and induction of HLA-DR antigen expression.

Human recombinant gamma-interferon (rhu-IFN-gamma) and human recombinant alpha-interferon (rhu-IFN-alpha 2 arg) with a chemical purity of over 95% were compared for their antiproliferative and HLA-DR-inducing activity in five human breast cancer cell lines (BT 20, ZR 75.1, MCF 7, 734B, Hs578T). Cytostatic effects on tumor cells were evaluated in monolayer cultures. HLA-DR antigen expression was examined by an indirect immunofluorescence technique using two different anti-HLA-DR monoclonal antibodies (anti-HLA-DR, VID-1) against framework determinants. rhu-IFN-gamma and rhu-IFN-alpha 2 arg differed in their antiproliferative efficiency in terms of both dose dependency and the spectrum of sensitive target cells. Combinations of rhu-IFN-gamma and rhu-IFN-alpha 2 always resulted in higher cytostatic effects. HLA-DR expression was exclusively inducible by rhu-IFN-gamma and did not correspond to its antiproliferative activity. Furthermore, HLA-DR expression did not depend on proliferation but did require intact RNA and protein syntheses as shown by inhibition with cycloheximide and actinomycin D. HLA-DR antigen expression in mammary cancer lines was dependent on time, dose, and the continued presence of rhu-IFN-gamma. Thus, our data suggest that in particular combinations type I and type II interferons might be useful in the treatment of breast cancer because they provide effective cytostatic and cell membrane-modulating properties.

Antibodies, Monoclonal↗

Testicular needle biopsy in diagnosis of infertility.

Testicular needle biopsies were performed on 10 patients who at the same time underwent open testicular biopsy. The tracts and puncture sites were explored on each of these patients, and an open biopsy was obtained at the puncture site simultaneously. Both needle specimen and open tissue specimen were fixed in Bouin solution and sent for histologic examination. In none of the cases was there found to be bleeding or extrusion of the testis at the puncture site. In one of the needle specimens, however, insufficient tissue was obtained for diagnosis. In the other 19 specimens, diagnostic accuracy was not compromised by the technique. The main differences appear to be fewer tubules obtained by the needle technique as well as decreased preservation of the interstitial tissue. This is a rapid, simple, and inexpensive method for testes biopsy which has proved to be both safe and diagnostically accurate.

Biopsy, Needle↗

Update: varicocelectomy--a safe outpatient procedure.

One hundred ninety-two males with palpable varicoceles and subfertility who underwent varicocelectomy were studied. Fifty-five patients underwent inpatient varicocelectomy and 137 ambulatory varicocelectomy. We have shown that ambulatory varicocelectomy is safe and effective. Surgical success is not compromised. Most importantly, outpatient varicocelectomy is extremely cost-effective. The average cost of ambulatory varicocelectomy was less than 25 per cent that of an equivalent inpatient procedure, with a mean cost of $372 and $1,536 per person, respectively.

Adult↗

[Surface glycoproteins of normal and malignant leukocytes].

This study aimed to evaluate the molecular weight distribution patterns and the quantitative expression of surface glycoproteins (S-GP) of various differentiation stages of human leucocytes. S-GP were first exposed by treatment with neuraminidase; subsequently they were labelled by galactose-oxidase treatment followed by reduction with 3H-sodium borohydride. Labelled S-GP were separated on polyacrylamide gels in the presence of SDS and were visualized by means of fluorography. A total of 8 major S-GP bands with apparent molecular weights of 230 000, 215 000, 200 000, 185 000, 175 000, 150 000, 125 000 and 110 000 daltons were identified. All of these S-GP were already expressed at the level of pluripotent myelopoietic stem cells but different in their relative expression during further cellular maturation.

B-Lymphocytes↗

Hydronephrosis and polycythemia.

Polycythemia is consistently produced in animals undergoing experimental hydronephrosis. This hematologic response is thought to be mediated by a microcirculatory insult and a more accelerated elaboration of erythropoietin by the hydronephrotic kidney. While an association between hydronephrosis and polycythemia has been reported in humans, it is a relatively rare event. Further studies are necessary to explain why this should be so, as well as to confirm that the polycythemia in humans is secondary to an increased production of erythropoietin.

Adult↗

The pathologic effect of ureteral ligation, with clinical implications.

Inadvertent, ureteral ligation is a frequent occurrence with pelvic surgery. We determined the effect of the ureteral ligation of varying lengths of time in an animal model in order to provide a rational basis for the clinical management of such injuries in humans. In the rat, simple deligation of a ureter that has been ligated for as long as 24 hours results in complete resolution of the injury with no gross or microscopic evidence of the trauma. After 48 and 72 hours of ligation, hydroureter was apparent.

Animals↗

Postvoid film of intravenous pyelogram in diagnosis of urethral diverticulum.

Urethral diverticulum is a correctable cause of lower urinary tract symptoms in women. It has been found to be present in from 1.85 to 4.7 per cent of all females. The postvoid film of the intravenous urogram (IVP) is the simplest and least invasive method available to diagnose urethral diverticula. It should be a routine part of the IVP in women with lower urinary tract symptoms.

Adult↗