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Biomedical subjects

J Ladefoged

Publications and source records attributed to J Ladefoged.

At least 37 records · Page 2Linked to original sources
PubMed1993

Acute effects of FK506 and cyclosporine A on cultured human proximal tubular cells.

The effects were studied of FK506 and cyclosporine A on human proximal tubular cells. An in vitro assay was used with cultured renal cells which displayed characteristics of proximal tubular cells. Cell growth was measured by [3H]thymidine uptake. FK506 inhibited cell growth by about 50% at 1 micrograms/ml but cells were not killed as shown by the dye exclusion test. The growth rate of cells recovered to control levels after removal of FK506 from the cultures. FK506 and cyclosporine A showed an additive effect on tubular cell growth reduction. This effect was similar at equivalent doses of FK506 and cyclosporine A, whereas in cultures of leukocytes, the half maximal response to mitogen was obtained at 0.01 micrograms/ml FK506 and 0.5 micrograms/ml cyclosporine A, respectively. Immunocytochemistry demonstrated that FK506 reduced the expression of interferon-gamma induced major histocompatibility complex (MHC) class I on the proximal tubular cells, but had no effect on the expression of the MHC class II antigens or the intercellular adhesion molecule (ICAM-1) on the cultured cells.

Cell Adhesion Molecules↗
PubMed1993

Parathyroid hormone dependent T cell proliferation in uremic rats.

Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA was normalized. Rat PTH 1-84 stimulated in vitro the PHA-induced proliferation of T cells in a dose dependent manner. This effect was significant in CRF rat lymphocytes, but not in lymphocytes obtained from normal rats. Based upon the present results it is suggested that the secondary hyperparathyroidism in chronic uremia is responsible for the enhanced proliferative response to PHA of T cells from CRF rats.

Animals↗
PubMed1993

A model of reversible uremia employing isogenic kidney transplantation in the rat. Reversibility of secondary hyperparathyroidism.

Kidney transplanted patients with normalized kidney function may still exhibit a variety of problems such as bone problems, vascularly problems, and hormonal dysfunctions. A part of the symptoms may be persisting uremic symptoms, secondary to the pretransplanted period of chronic uremia. An experimental rat model, designed to the study of the reversibility of the chronic uremic implications is therefore described. A stable, severe chronic uremia was induced by 5/6 nephrectomy to inbred Lewis rats. Ten weeks later uremia was reverted by a successful isogenic rat kidney transplantation. During the period of chronic uremia the p-urea was elevated to an average of 21.8 +/- 0.9 mmol/l and p-creatinine to 105.7 +/- 5.7 microM/l. The isogenic kidney transplantation resulted in reestablishment of normal kidney function with an average level of p-urea of 7.6 +/- 0.2 mmol/l and p-creatinine 42.5 +/- 1.9 microM/l perfectly corresponding to the sham-operated rats, i.e. one-kidney rats. Reversibility of the secondary hyperparathyroidism due to chronic uremia was investigated in the model. In rats with chronic renal failure PTH increased from 52 +/- 4.9 pg/ml to 152 +/- 12.2 pg/ml and was normalized after transplantation. It is therefore concluded that the present described technique of introducing long term uremia followed up by a successful kidney transplantation in the rat may be a useful model to study the reversibility of different uremic manifestations.

Animals↗
PubMed1992

Kidney functioning during lithium treatment: a prospective study of patients treated with lithium for up to ten years.

A cohort of 53 patients with affective disorders who originally carried through renal functional tests before start of prophylactic lithium treatment were followed up prospectively after an average period of 8.5 years (range 7-10 years). Ten patients who had continued lithium treatment were re-examined. In this subgroup, the glomerular function was unaffected by the treatment, whereas the average urine volume increased during lithium treatment (NS). Polyuria and low renal concentrating abilities were also found before start of treatment and these findings underline the importance of access to renal baseline information prior to lithium treatment.

Adult↗
PubMed1992

Human proximal tubular cells modulate allogen responses of leukocytes in vitro.

The interaction between proximal tubular cells and leukocytes was examined. In co-cultures of tubular cells and allogenic leukocytes, tubular cells expressed MHC antigens and ICAM-1. A small number of leukocytes adhered to tubular cells and induced cytotoxic damage. Thus, 65% of the tubular cells were viable after co-culturing with allogenic leukocytes. These cells had low alloreactive capacity, which was not due to lack of interleukin-1 or interferon-gamma. The presence of tubular cells modulated the immune response of leukocytes by reducing the effect of mitogen by 80%, allogens by 65% and interleukin-2 by 40%. A soluble factor released in the co-cultures was a likely mediator, since addition of supernatants from co-cultures suppressed mitogen responses by 27% compared to leukocytes cultured alone. This mediator might be prostaglandin, because addition of indomethacin to co-cultures increased the growth response of leukocytes.

Cell Adhesion Molecules↗
PubMed1991

[The significance of brain death as a criterion for renal transplantation. Status after 9 months].

The effect of introduction of the brain-death criterion in Denmark on the course of cadaver kidney transplantation was evaluated by comparing the course of 31 consecutive patients transplanted after introduction of brain-death criterion with the course of a similar consecutive group of patients transplanted just before the new death criterion. The consequences of the new death criterion were significantly earlier onset of graft function, diminished need for posttransplant dialyses, reduced need for immunosuppressive treatment with Minnesota-antilymphocytglobulin and briefer hospital stays. The easier postoperative course had great psychological effects for the patients and the staff, and the cost of each transplantation was estimated to be reduced by at least 50,000 DKr per patient (approximately 5,000 pounds).

Brain Death↗
PubMed1991

Production of prostaglandin E2 by macrophages in uraemia.

Production of prostaglandin E2 (PGE2), interleukin-2, and response to lectin stimulation were examined in peripheral blood mononuclear cell cultures from 46 patients on haemodialysis, 20 patients on continuous peritoneal dialysis, 18 non-dialysed patients with mild to moderate renal failure, and 52 control subjects. Production of PGE2 and responses to phytohaemagglutinin (PHA) were decreased in cell cultures from patients on dialysis. Similarly, production of interleukin-2 was significantly reduced in patient groups as compared to control subjects, but there was no relationship between production of PGE2 and responses to PHA or production of interleukin-2. Addition of exogenous indomethacin did not return the response to normal and the patient cultures were not more sensitive to exogenous PGE2 than the control cultures. Thus, release of PGE2 does not account for the impaired in vitro response of uraemic lymphocytes.

Dinoprostone↗
PubMed1991

Glomerular tip lesions in renal biopsies with focal segmental IgM.

Renal biopsies in which immunohistologic examination had shown the presence of glomerular focal segmental IgM were reviewed in order to investigate the histology and clinical course in these patients. Among 19 such biopsies, 12 had focal segmental glomerulosclerosis (FSGS), whereas seven had only so-called glomerular tip lesions (GTL). GTL also occurred moreover in four of the patients with FSGS. Clinical data suggest a somewhat milder course of disease in the seven patients with GTL as the sole lesion than in the patients of the FSGS group. The nature of GTL is at present unclear. We suggest that GTL may be an initial stage of FSGS, being a lesion that may or may not develop towards FSGS in its typical form. Regardless of its origin, attention is directed to the GTL as a characteristic histologic glomerular lesion, which may be the only significant histologic change in the renal biopsy from a patient with nephrotic syndrome or severe proteinuria.

Adult↗
PubMed1991

Lithium: long-term effects on the kidney. A prospective follow-up study ten years after kidney biopsy.

Forty-six patients with recurrent affective disorders, who began prophylactic treatment with lithium an average of 20 years previously, were followed up prospectively after a ten-year observation period to assess renal function. Nineteen patients had maintained lithium therapy, and eight patients had died. Tubular function was almost unchanged and patients who had continued lithium had not shown increasing urine volumes, but patients who had received lithium in a single daily dosage at night had a significantly lower urinary output than those on a multiple-dosage schedule. The GFR decreased significantly, but the decline was essentially dependent on increasing age, except in two patients who had developed renal insufficiency. Renal function during chronic lithium treatment is related to age, lithium intoxication episodes, pre-existing renal disease, and treatment schedule rather than to duration of prophylactic lithium therapy.

Adult↗
PubMed1991

Is initial (24 hours) lavage necessary in treatment of CAPD peritonitis?

A randomized trial was conducted to examine the influence of initial lavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty-six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including either initial 24 hours lavage before resumption of routine CAPD schedule (prior standard approach) or continued prolonged exchanges as in routine CAPD schedule. Median time to solved infection (normalization of white cell count in dialysis effluent) was identical (3 days) in the two groups. Treatment success rate was found to be 72% in the group with initial lavage and 89% in the group with prolonged exchanges. The difference in treatment success (17%) in favour of continued CAPD schedule was not found significant (95% confidence limits--1% to 35%). The results suggest lavage to be of no clinical benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock.

Acute Disease↗
PubMed1990

Accessory cell functions in mononuclear cell cultures uremic patients.

Mononuclear cells (PBMC) were isolated from dialyzed patients and healthy control subjects. Lymphocyte responses to stimulation with optimal and suboptimal concentrations of lectin (PHA), or stimulation with T cell receptor antibody (Leu 4) were found decreased in the patient cultures. The separate and the combined effects of exogenous interleukin-1 (IL-1) and interleukin-2 (IL-2) were examined in PHA and Leu 4 stimulated cell cultures. Addition of IL-1 did not normalize the decreased proliferation response of the patient cultures. In contrast, addition of IL-2 alone clearly enhanced and almost normalized the response of patient cultures stimulated with suboptimal concentrations of PHA. The combined addition of IL-1 and IL-2 gave no evidence of an additive effect of IL-1 and IL-2. Cell cultures from uremic and normal HLA-identical relative were examined. Substitution of uremic adherent monocytes with normal adherent monocytes as accessory cells did not improve the uremic T cell responses to stimulation with PHA. Furthermore, uremic adherent cells did not suppress the normal T cell responses. These results suggest that uremic accessory cells support T cell activation and, in particular, do not suppress T cell responses. The effect of IL-2 in the present study as well as previous findings of decreased IL-2 production in patients cultures may indicate that uremia primarily influences the proliferation of T cells.

Antigen-Presenting Cells↗
PubMed1990

Candida norvegensis peritonitis and invasive disease in a patient on continuous ambulatory peritoneal dialysis.

We report a case of Candida norvegensis invasive disease in an immunosuppressed renal transplant patient on continuous ambulatory peritoneal dialysis. Multiple cultures of peritoneal fluid, blood, and tracheal suction done over a 2-week period were positive for this unusual isolate. Despite treatment with amphotericin B and flucytosine the patient died. This is the first report of C. norvegensis fungemia documented by culture.

Adult↗
PubMed1990

Release and effect of prostaglandin E2 in cocultures of lymphocytes and human tubular cells.

Prostaglandin E2 reduced the expression of HLA-ABC as well as HLA-DR antigens in cultured human tubular cells, when cells were stimulated by gamma-interferon. The PGE2 release was low in tubular cell cultures, but highly increased by coculture of tubular cells and allogeneic lymphocytes, compared to cultures of unstimulated lymphocytes, or to cocultures with autologous lymphocytes. Cocultures between non-adherent mononuclear cells and tubular cells produced low amounts of PGE2, whereas cocultures of adherent monocytes and tubular cells produced equal as much PGE2 as cultures made with stimulated peripheral blood leucocytes. The adherent cells were dominated by macrophages. The proliferative response of lymphocytes in cocultures with tubular cells was low, and was increased by indomethacin. The results indicated, that presence of monocytes adherent to the tubular cells in cocultures, down-regulate the proliferative response of allogeneic lymphocytes to the tubular cells, which may in part attribute to an inhibitory effect of PGE2.

Cell Adhesion↗
PubMed1989

Long-term effects of lithium on the kidney: functional-morphological correlations.

Correlations between quantitative kidney biopsy findings and clinical renal function in 46 unselected patients treated with lithium for an average of eight years were studied. A significant relationship between maximum renal concentrating capacity and degree of tubular atrophy was found. GFR correlated significantly with sclerotic glomeruli as well as atrophic tubules in patients on a multiple dosage schedule, whereas no relationship was seen in patients receiving lithium in a single daily dose. Thus, renal dysfunction may have a structural basis in a subgroup of lithium-treated patients on a multiple dosage schedule.

Adult↗
PubMed1988

Mitogen-induced lymphocyte transformation in four different serum-free media.

The proliferative responses of lymphocytes induced by the mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (ConA) were tested in four different serum-free lymphocyte culture media in which serum was replaced by commercially produced serum substitutes. Two of the serum-free lymphocytes cultures (SF-X and FEB-100) achieved proliferative responses to PHA and PWM comparable with those obtained in medium containing fetal calf serum, but only when the cell number was increased, whereas none of the lymphocyte cultures in serum-free medium showed adequate proliferative responses to ConA stimulation. The essential factors in serum-free media for optimal growth and mitogen stimulation of lymphocytes include insulin, transferrin, electrolytes, glutamine and a high cell concentration.

Blood Substitutes↗
PubMed1988

Renal handling of cathodic trypsin-like immunoreactivity in man.

The renal handling of cathodic trypsin-like immunoreactivity (TLI) was examined in 60 healthy persons (group I), 59 patients with proteinuria (group II), 7 healthy men receiving intravenous lysine to partially inhibit renal tubular protein reabsorption (group III) and 20 patients who underwent diagnostic renal vein catheterization (group IV). The urinary TLI concentration and TLI ratio (TLI clearance divided with creatinine clearance) were higher in group II than group I (p less than 0.001, Mann-Whitney test). In group II negative correlations were present between serum TLI and creatinine clearance (Spearman's rho = -0.84, p less than 0.001) and between TLI ratio and creatinine clearance (rho = -0.76, p less than 0.001). In group III the renal TLI clearance was undetectable before lysine but increased to a maximal median value of 4.00 ml/min per 1.73 m2 (range: 2.44-9.25 ml/min per 1.73 m2) after lysine. In group IV, the renal arterio-venous extraction of TLI was correlated to inulin extraction (rho = 0.85, p less than 0.001). The glomerular filtrability (the ratio between TLI and inulin extractions) was median 0.53 (range: 0.13-0.94). In conclusion, TLI has a high glomerular filtration and an almost complete tubular reabsorption and catabolism (with normal kidney function).

Adult↗