Identification of virus resistant tumor cell subpopulations in three-dimensional uveal melanoma cultures.

To better understand melanoma resistance to herpes simplex virus type 1 (HSV-1)-mediated oncolysis, traditional two-dimensional (2D) cultures and extracellular matrix (ECM) containing three-dimensional (3D) cultures of OCM1 and C918 uveal melanoma cells were infected with an HSV-1 strain that expresses the green fluorescent protein (GFP) marker during replication. Although 2D cultures were completely destroyed within a few days of HSV-1 inoculation, viable GFP-negative tumor cells remained detectable in 3D cultures for several weeks. Tumor cells with increased resistance to HSV-1 included cells that formed vasculogenic mimicry patterns and multicellular spheroids and cells that invaded Matrigel individually. Mechanisms of tumor resistance against HSV-1 in the 3D environment included impaired virus spread in the ECM and ECM-mediated inhibition of viral replication after viral entry into tumor cells. Observations also suggested that HSV-1 established quiescent infection in some tumor cells present in multicellular spheroids and that this could revert to productive viral infection when the tumor growth pattern changed. These findings indicate that 3D tumor cell cultures can be used to identify distinct tumor cell populations with increased resistance to HSV-1 and to explore mechanisms of ECM-mediated tumor resistance to oncolytic virotherapy.

Effects of dopamine and aminophylline on contrast-induced acute renal failure after coronary angioplasty in patients with preexisting renal insufficiency.

In phase 1 of this study, 60 patients undergoing coronary angioplasty were randomized to receive saline, dopamine, or aminophylline; the overall incidence of contrast-induced renal failure was 38%, without difference among the 3 groups. In phase 2 of this study, 72 patients with established contrast-induced renal failure were randomized to receive saline or dopamine; dopamine had a deleterious effect on the severity of renal failure, prolonging the course.

Vancomycin-induced toxic epidermal necrolysis.

We have reported a patient who had had renal transplantation for end-stage renal disease; she was treated for fever and presumed sepsis with intravenous tobramycin and vancomycin, with subsequent development of persistent fever, eosinophilia, and a maculopapular rash that progressed to linear bullae. Findings on skin biopsy were consistent with a diagnosis of toxic epidermal necrolysis. Sustained measurable serum concentrations of vancomycin, the temporal response to drug exposure, and the response to steroid therapy suggest vancomycin as the causative agent.

Zinc balance in combined zinc deficiency and uremia.

In order to evaluate whether the hypozincemia associated with chronic renal failure represents true negative zinc balance, male Lewis rats were randomized and pair-fed zinc replete (+Zn) or deplete (-Zn) diets. Subsequently, each animal underwent one- and two-thirds nephrectomy, or a sham operation. Complete balances for zinc, calcium, and magnesium were determined weekly before and after nephrectomy. At sacrifice, -Zn animals had significantly lower (P less than 0.005) plasma zinc levels compared to controls. Nephrectomized (N) animals had significantly elevated plasma creatinine (P less than 0.005), diminished creatinine clearances (P less than 0.005), and increased urinary flows (P less than 0.005) and protein excretion (P less than 0.01) compared to sham-operated (S) controls. Zinc nutritional status had no effect on these parameters in animals with comparable renal function. -Zn/N animals had consistently significantly elevated (P less than 0.005) urinary zinc excretion compared with -Zn/S with similar plasma zinc concentrations. Urinary zinc excretion correlated with urinary flow (r = 0.739, P less than 0.005), urinary protein (r = 0.635, P less than 0.01) and urinary calcium excretion (r = 0.855, P less than 0.005) in -Zn groups. -Zn/N rats had a significantly larger fecal zinc excretion for the first week post-nephrectomy, compared to -Zn/N controls (P less than 0.005). This resulted in negative zinc balance in -Zn/N animals, compared to their pre-nephrectomy balance (P less than 0.05) or to -Zn/S controls for the first (P less than 0.005) and second (P less than 0.05) weeks. -Zn/N rats had lower (P less than 0.02) hepatic zinc concentrations compared to the -Zn/S group.(ABSTRACT TRUNCATED AT 250 WORDS)

Thymic functions in uremic rats: evidence for thymosin alpha 1 deficiency.

Changes in the circulating lymphocyte populations and thymus glands were studied in rats with experimental chronic renal insufficiency (CRI). Compared to normal or sham-operated animals, rats with CRI had significant reduction in the percentages of circulating T and B lymphocytes. CRI was also associated with marked thymic atrophy and reduction in the numbers of small cortical and medullary thymic lymphocytes. Quantitative microfluorometry revealed a significant reduction in the intrathymic concentration of a potent immunomodulator, thymosin alpha 1 in all uremic animals. There was a significant positive correlation between the percentages of circulating T lymphocytes and the intrathymic concentrations of thymosin alpha 1.

Glomerulocystic kidney disease. Report of an adult case.

A case of glomerulocystic kidney disease (GCK) in an adult is reported. The patient described here had no other congenital malformations, and there was no family history of renal disease. The histopathologic findings support the glomerular origin of GCK. This case illustrated that GCK may be associated with stable renal function for many years. In view of this, GCK should be considered in the differential diagnosis of cystic kidney disease in the adult.

Acute myelomonocytic leukemia associated with nephrotic syndrome. A case report with immunological studies.

A patient with acute myelomonocytic leukemia (AML) developed nephrotic syndrome. The renal biopsy showed focal glomerulosclerosis by light microscopy. Electron microscopy and immunofluorescence revealed electrondense deposits, IgG and C'3 in the glomerular mesangium. A 21S circulating immune complex (CIC) present in the patient's serum and the renal biopsy eluate contained immunochemically identical materials. The isolated antibodies from the 21S CIC and the eluate showed restricted reactivity against autologous AML cells. Immunodiffusion studies demonstrated common antigenicity between the 21S CIC antigen, the eluted antigen and between autologous AML cell membrane antigens.

Immunological properties of peptic fragments of bovine serum albumin.

The effect of peptic degradation on the immunological and antigenic properties of bovine serum albumin (BSA) was investigated. Molecular fragments obtained after various times of digestion (3-360 min) were studied. Enzymatic digestion resulted in a rapid loss of serologically defined antigenic determinants. The immunogenicity of the fragments as measured by the level of reaginic and total anti-BSA antibody response in BDF1 mice was also diminished. Pre-treatment of mice with fragments exhibiting a low density of B-cell interacting determinants before immunization with BSA, resulted in significant suppression of both the primary and secondary antibody response. The most effective immunosuppressive fragments were obtained following removal of peptides which bound to anti-BSA antibodies. The suppression was shown to be antigen specific. It was concluded that separate determinants on the BSA molecule were responsible for the immunogenic and suppressive properties of the antigen.

The delayed appearance of an antinuclear factor and the diagnosis of systemic lupus erythematosus in glomerulonephritis.

In 11 patients who presented with apparently idiopathic glomerular disease the antinuclear factor (ANF) was absent initially but was eventually detected during observation extending over 6 years. In 4 patients a diagnosis of systemic lupus erythematosus (SLE) has now been made and the disease treated. Of the remaining 7, 2 had conditions known to be associated with a positive ANF, and in 4, drug therapy induced the ANF. Clinical features, complement studies and measurement of anti-DNA antibody were of value in distinguishing those patients with SLE from the others.

The treatment of lupus nephritis by methyl prednisolone pulse therapy.

Four patients with proliferative glomerulonephritis due to systemic lupus erythematosus were treated with intravenous methyl prednisolone 'pulse' therapy. In all, eight courses of therapy were given, three for acute oliguric renal failure; and on each occasion there was a good response to the treatment. Clinical, histological and immunological details of the patients are presented. The diagnosis, treatment, and monitoring of disease activity in lupus nephritis are discussed in the light of this experience.

Detection, significance and treatment of paraprotein in patients presenting with 'idiopathic' proteinuria without myeloma.

This paper describes the detection of a paraprotein in blood or urine in 12 of 260 patients with 'idiopathic' proteinuria, most of whom presented with the nephrotic syndrome. None had myeloma at presentation and only two have developed it. Initial clinical and biochemical findings did not suggest paraprotein-associated disease, total serum globulins and individual immunoglobulin levels usually being in the normal range. In seven of the 12 cases the paraprotein was detected only after repeated analysis of serum and urine specimens over months or years. Renal histopathology varied from case to case and is described in detail; amyloid deposition did not occur in patients who excreted kappa chain Bence Jones protein and was extensive in only three. One of these eventually developed myeloma. Patients were aged 27--69 years at onset and were observed without specific therapy for up to 56 months. Glomerular filtration rate tended to decline and proteinuria persisted. All patients have now been treated by a chemotherapeutic regimen consisting of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone, in repeated short courses. In some patients, particularly those who had kappa Bence Jones protein, there was striking improvement. Overall survival is good, eight patients being alive 17--90 months after the onset of symptoms. The importance of repeated search for paraprotein in apparently idiopathic renal disease in adults is emphasized.