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Biomedical subjects

J L Bernheim

Publications and source records attributed to J L Bernheim.

At least 37 records · Page 2Linked to original sources

Minimal-change nephropathy and malignant thymoma.

A 56-year-old man had fever, precordial pain, and a mediastinal mass. The mass disappeared two months later and the patient remained asymptomatic for 2 1/2 years. At that time a full-blown nephrotic syndrome developed, with minimal-change glomerulopathy. The chest x-ray film showed the reappearance of a giant mediastinal mass. On biopsy of the mass, malignant thymoma was diagnosed. Association between minimal-change disease and Hodgkin's disease is well known, while the association with malignant thymoma has not been previously reported. The relationship between malignant thymoma and minimal-change disease is discussed, and a possible pathogenic mechanism involving cell-mediated immunity is proposed.

Humans↗

[Leiomyoma of the small bowel with hypercalcaemia: presence of a substance with parathormone activity (author's transl)].

A leiomyoma of the small bowel produced laboratory features of hyperparathyroidism which disappeared promptly after tumour resection. Hypercalcaemia, hypophosphatemia, hyperchloremia, elevated chloride/phosphorus ratio, increased urinary cyclic AMP, and blood levels of immunoreactive parathormone were present. Electron microscopy showed dense round granules in the tumour cells.

Aged↗

Quantification of entry into and exit from the cell cycle in human lymphocyte cultures.

A mathematical model is presented for the analysis of transition between cycling and non-cycling compartments by cells responding to a growth stimulus. The cellular age distribution as a function of time is derived from sequential [3H]thymidine pulse labeling indices. Rates of entry into and exit from the cycling compartment are determined on the basis of labeling indices obtained after instantaneous and long duration [3H]thymidine pulses. Analysis of an experiment involving sequential measurements over the whole lifespan of a human lymphocyte culture stimulated by phytohemagglutinin is presented as an example of the application of this method.

Cell Cycle↗

DNA synthesis and proliferation of human lymphocytes in vitro. I. Cell kinetics of response to phytohemagglutinin.

The response of human lymphocytes to phytohemagglutinin (PHA) stimulation was assessed in detailed kinetic studies, in order to define conditions permitting and regulating proliferation. By utilizing live and dead cell counts, cell cycle characterizations, and calculations of rates of entry into S phase and mitosis, it was demonstrated that dilute culture conditions (2 X 10(5) cells/ml) enable lymphocytes to proliferate for a period of 5 or 6 days. Although cell division occurs in concentrated cultures (2 X 10(6) cells/ml), net proliferation is not demonstrable due to extensive cell death and earlier decay in the proliferative response. It is projected that without cell death the cell count would rise more than 6-fold in a dilute culture and 2-fold in a concentrated culture under these growth conditions. The kinetic analyses did not demonstrate separate PHA dose thresholds for blastogenesis and entry into S phase. High doses of PHA stimulated a suboptimal response by causing excessive cell death without reducing initial entry into the cell cycle. These results provide a kinetic explanation for the frequent observation of little net proliferation despite substantial 3H-thymidine incorporation in PHA-stimulated lymphocyte cultures. Cell death is identified as a parameter that must be considered in the interpretation of in vitro lymphocyte stimulation studies, and methods for quantifying the role of cell death are demonstrated.

Blood Cell Count↗

DNA synthesis and proliferation of human lymphocytes in vitro. II. Characterization of the DNA newly synthesized after phytohemagglutinin stimulation.

DNA newly synthesized by phytohemagglutinin-(PHA) stimulated human lymphocytes has been analyzed for the possibility that all DNA synthesis may not represent premitotic genome duplication. Equilibrium density gradient characterization of bromodeoxyuridine-(BUdR) substituted DNA demonstrates semi-conservative DNA replication, without evidence for repair synthesis. Experiments to detect selective replication (amplification) of a portion of the DNA involved measurement of reassociation kinetics as well as measurement of the kinetics of BUdR appearance in prelabeled DNA. The presence of large quantities of amplified DNA has been excluded, although amplification cannot be ruled out completely by these techniques. Finally, the kinetics of DNA release from dead lymphocytes is characterized, and factors tending to reduce the complexity of released, labeled DNA are identified.

Bromodeoxyuridine↗

Kinetics of cell death and disintegration in human lymphocyte cultures.

In order to quantitate lymphocyte proliferative responses, we explored the role of cell death in the kinetics of phytohemagglutinin-stimulated cultures. Unless the disintegration time (tDIS) of nonviable lymphocytes in culture is known, the rate of cell death cannot be calculated. To obtain tDIS, we determined the time interval between total and viable cell population decay after various killing events. Two subpopulations of lymphocytes were observed, the major (80%) with a mean (+/-SEM) tDIS of 16+/-2 hr and the minor (20%) with a tDIS of 45+/-7 hr. Kinetic balance sheets were constructed predicting total culture DNA content (cells plus medium), as calculated both from proliferation rates and from observed death and disintegration rates. In an experiment characterized by extensive cell death, the two tallies were well-matched when the above data were utilized. The large discrepancy between predicted and observed DNA contents of the medium indicates that the DNA of disintegrated lymphocytes is extensively degraded. We conclude that cell death explains proliferation deficits in stimulated lymphocyte cultures. Our approach to quantitation of cell death may have general applicability to kinetic studies of cultured cells.

Cell Division↗

Inhibition of human lymphocyte stimulation by steroid hormones: cytokinetic mechanisms.

The steroid hormones estradiol, progesterone and testosterone, in addition to cortisol, inhibited stimulation of human peripheral blood lymphocytes by phytohaemagglutinin (PHA) and Con A. This effect upon lymphocyte transformation was assayed by three methods: quantitation of [3H]thymidine incorporation into acid precipitable material, microscopic assessment of blastic transformation and determination of the labelling index. Addition of steroid hormones at the initiation of culture resulted in a marked inhibition in all three parameters, which was observed with lower concentrations of cortisol than the other hormones. The inhibition was not attributable to cell death and could be partially reversed by removing hormones from the incubation medium after culture for 48-72 hr. Late addition of steroid hormones, 52 hr after addition of mitogen and 18 hr prior to pulse-labelling with [3H]thymidine, also resulted in reduced [3H]thymidine incorporation, accompanied by a nearly 50% reduction in the labelling indices and only a minimal decrease in the per cent transformed cells. Inhibition of lympohcyte stimulation by steroid hormones operates by the following cytokinetic mechanisms: (1) suppressed recruitment of cells from G3 to G1 phase of the cell cycle, as indicated by the diminished per cent blasts; (2) inhibition of progression from G1 phase into S phase, as evidenced by the reduced ratio [labelling index/blasts]; and, in the case of estradiol and progesterone, (3) reduced rate of DNA replication or altered intracellular [3H]thymidine specific activity as shown by the decreased ([3H]thymidine incorporation/labelling index) ratio. Late addition of steroid hormones to stimulated cultures reduced the per cent of cells in S phase, but did not revert previously transformed cycling lymphocytes to the G3 state.

Cell Division↗

Apparent total alpha1-antitrypsin deficiency: report of a case.

A 29-year-old female, with chronic renal failure and chronic bilateral emphysema, was admitted with severe uremia and septicemia secondary to multiple abscesses in the right kidney. Her condition improved after right nephrectomy. Pulmonary function studies showed marked obstructive and restrictive lung disease consistent witht the diagnosis of primary emphysema. On biochemical and histological examination, the liver was found to be normal. Alpha1-antitrypsin could not be demonstrated in the patient's serum at normal pH by any of the known techniques, but protein molecules with alpha1-antitrypsin antigencity were found at pH 4.8; this suggests a pH-dependent structural difference in alpha1-antitrypsin protein. Starch gel electrophoresis gave a multibanding pattern not previously described. A new form of apparent total alpha-1-antitrypsin deficiency is postulated.

Abscess↗

[Renal venous thrombosis in the adult].

Eleven cases of renal vein thrombosis (RVT) are reported, 9 of which presented with nephrotic syndrome (NS) and 2 with acute renal failure (ARF). Hematuria, enlarged kidneys, assymetric peripheral edema and collateral vein dilatations were the classic symptoms. Phlebography was employed in 101 suspected cases and permitted definitive diagnosis in 11 percent. Phlebography was performed in 13 percent of the NS cases and 11 percent of the ARF cases, but in none of the other cases. Fifteen kidney biopsies (KB) were performed in 8 patients, 6 with NS and 2 with ARF. In the 6 cases of NS, 4 presented a pattern of membranous glomerulonephritis and 2 had mild thickening of the basement membrane. This was confirmed by electromicroscopy in 5. In the 2 with ARF capillary dilatations, polynuclear infiltrates and interstitial edema was found. Repetitive KB, performed in 3 cases, revealed the same histological pattern in 2, while in the other case granular membranous deposits were found on the second biopsy that were not apparent in the first. This last patient was free from clinical manifestations at the time of this last biopsy. Immunofluorescent studies (iF) were performed on 7 KB of 5 patients, 4 with NS and 1 with ARF. Three of the 4 with NS presented a pattern of membranous deposits. On i.F one patient was found to have IgG and C3 deposits, one IgG and fibrinogen and one no detectable IgG, IgA, IgM, IgE, C3 or fibrinogen. The fourth with minimal histological changes was also negative for i.F, as was the case of ARF. Sequential treatment by heparin and antivitamin K was administered in 8 patients. Recovery occurred in 3 and stabilization in 4, while in 1 case this treatment was without effect.

Acute Kidney Injury↗

Hairy cell leukemia: functional, immunologic, kinetic, and ultrastructural characterization.

A diagnosis of hairy cell leukemia was made by optic microscopy, phase-contrast microscopy, electron microscopy, scanning microscopy, and histochemistry of the abnormal blood cells. In vivo these cells were found to have a half-time in the blood of approximately 150 hr. In vitro they had the capacity to adhere firmly to plastic, making it possible to obtain a pure population of hairy cells. Neither T-rosette formation nor phytohemagglutinin (PHA) transformation could be demonstrated in these cells. On the other hand, the presence of immunoglobulins on the surface of the hairy cells (HC) by immunofluorescence, and the synthesis and secretion by these cells of IgM type lambda-chains shown by radioimmunodiffusion, were in favor of their B-type lymphocyte origin. Similarities to chronic lymphocytic leukemia were apparent.

Bone Marrow↗