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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 307 records · Page 17Linked to original sources
PubMed1989

Purification and characterization of human recombinant precursor interleukin 1 beta.

We have purified the 31-kDa precursor of human interleukin 1 beta (proIL1 beta) from recombinant Escherichia coli expressing the protein. The recombinant precursor was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, spectroscopy, Western blot, and for biological and receptor binding activity. The protein migrates at the expected molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analytical gel filtration columns. The specific activity of the recombinant precursor is less than 10(2) units/mg in the EL4 thymoma assay compared with 5 x 10(8) units/mg for the recombinant 17-kDa mature protein. The inactivity of the precursor is attributable to the inability of the protein to bind the IL1 receptor on EL4 cells as shown by receptor competition studies using 125I-labeled 17-kDa IL1 beta. Inactivity of the IL1 beta precursor is not due to degradation of the protein in either the bioactivity or receptor binding assays. The inactive IL1 beta precursor is converted to an active form following proteolysis with chymotrypsin which generates a carboxyl-terminal fragment of 17 kDa that is 6 orders of magnitude more active than the starting IL1 beta precursor. Removal of the first 114 amino acids from proIL1 beta generates a fully active molecule. In contrast, removal of the first 77 amino acids by treatment with trypsin only partially restores activity. The resultant 22-kDa protein exhibits a 600-fold increase in both biological and receptor binding activity, demonstrating a direct correlation between the ability of sequences within the pro-region to inhibit biological activity and inhibit binding to the IL1 receptor. Far-UV circular dichroism spectroscopy indicates that proIL1 beta is similar in secondary structure to mature IL1 beta; both proteins are nonhelical beta sheet proteins.

Circular Dichroism↗
PubMed1989

Nasal irritation and pulmonary toxicity of aliphatic amines in mice.

The expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during a 15-min oronasal exposure to increasing concentrations of twenty aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, eight out of the twenty amines were tested for pulmonary toxicity in mice and for the effects of a 120-min exposure on the respiratory rates of non-anaesthetized, tracheally cannulated mice (RD50TC). Both allylamine and diallylamine showed RD50 values of 9 ppm and 4 ppm, respectively, while the RD50 values associated with exposure to saturated amines ranged from 50 to 200 ppm. Among the eight amines tested for both upper airway irritation and pulmonary toxicity, diisopropylamine and di-n-butylamine showed a RD50TC/RD50 ratio of less than 1, indicating that the respiratory toxicity induced by these two amines would be related primarily to pulmonary effects. On the basis of prior predictions proposed for upper airway irritants, tentative standards are given for ten amines. Moreover, it is suggested that the basis of standards for industrial exposure to diisopropylamine and di-n-butylamine should be specified.

Amines↗
PubMed1989

Demonstration of spontaneous XX/XY chimerism by DNA fingerprinting.

The M13 bacteriophage probe, which makes possible the establishment of DNA fingerprints, was used to study a phenotypically normal woman with a 46XY karyotype and her twin brother. Identical fingerprints and positive hybridization with a series of Y-specific probes were obtained on blood samples from the siblings. DNA from a skin biopsy of the woman yielded a clearly different pattern and displayed no Y-specific hybridization, indicating that she is a spontaneous chimera. This study illustrates the use of DNA fingerprinting as a powerful and simple aid to the diagnosis of natural chimerism.

Adult↗
PubMed1989

Diagnostic cordocentesis: two years of experience.

The first diagnostic cordocentesis was performed in our unit in October 1985, our 2-year experience is reported. 144 samplings were performed in 137 patients (139 fetuses - 2 patients had twin pregnancies) during gestational weeks 14 to 42. The first attempt was successful in 80% of the procedures, 4 samplings failed. There were no fetal deaths within 3 days after diagnostic cordocentesis, a transient fetal bradycardia was observed in 12.2% of the cases, bleeding occurred in 13.6% of the cases. The indications for cordocentesis were: risk of fetal infection, karyotyping, hemophilia A, alloimmunisation, search for paternity, assessment of fetal acid-base status. Our data confirm that cordocentesis is a safe and reliable diagnostic procedure providing guidelines for management of the pregnancy.

Blood Specimen Collection↗
PubMed1989

Frequency of development of early cortical scarring in acute primary pyelonephritis.

Fifty-five cases of primary (that is, without urinary tract abnormalities), acute pyelonephritis (PN) were studied by computed tomodensitometry (CT). There were 48 women and 7 men. All were febrile and 16 had positive blood cultures. In 7 cases, (4 diabetics and 3 malnourished alcoholics) PN was painless, diagnosis was delayed and lesions were severe. Two diabetics underwent emergency nephrectomy for sepsis. Conventional radiological techniques (IVP and ultrasonography) were poorly informative. In contrast, initial CT abnormalities were visible in 44 patients. They consisted of triangular or round hypodense images, diffuse hypodensity in a grossly swollen kidney, and/or abscesses. Hypodense images were presumably due to acute focal ischemia. Renal histology was available in five patients. It showed acute interstitial nephritis with leukocyte infiltrates, edema and hemorrhagic streaks. Pyelonephritis was due to E. coli in 48 cases (87.5%). In 27 cases E. coli isolates were studied by genotypic assays which detect the three most frequent (pap, afa and sfa) of the four operons known to encode adhesin. In all cases, at least one of these genotypic markers of uropathogenicity was found. In 27 cases, repeat CT was done shortly after treatment. It showed healing in only 12. Early cortical scar formation was visible in 2. Final evaluation in 27 cases with adequate follow-up showed that (in addition to the 2 patients who had been nephrectomized), in only 17 of 27 (63%) had the kidneys recovered a normal appearance. In two cases one kidney had undergone atrophy; renal biopsy showed subacute-chronic interstitial nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Buspirone and diazepam: comparison of subjective, psychomotor and biological effects.

The effects of oral buspirone (BUS, 10 mg) and diazepam (DZP, 10 mg) were studied in 12 healthy women volunteers using subjective ratings, objective tests of psychomotor and cognitive functions and urinary dosage of catecholamine output. Drugs were randomly administered to the same subjects, in a crossover, double-blind study, each drug administration being separated by at least 1 week. BUS subjective effects were less severe than those of DZP and not accompanied by feelings of sleepiness that characterized DZP sedative effects. Furthermore, BUS did not impair psychomotor functioning while DZP induced both an impairment of central sensory processing and, to a lesser extent, an impairment in delayed memory.

Arousal↗
PubMed1989

Patterns of plasma progesterone, androgen and oestrogen concentrations and in-vitro ovarian steroidogenesis during embryonic diapause and implantation in the mink (Mustela vison).

Peripheral plasma progesterone concentrations exhibited an increase 10 days before implantation, coinciding with the resumption of blastocyst growth and with a decrease in plasma androgen values (DHA, androstenedione, testosterone). No definite pattern of oestrone was observed and oestradiol concentrations remained undetectable. The production of steroids by dispersed luteal cells showed that the growth of the corpora lutea paralleled that of blastocysts and resulted in hypertrophy followed by hyperplasia of the luteal cell. The production of progesterone in the medium increased with blastocyst size up to implantation; it was enhanced by mink charcoal-treated serum, but prolactin, LH, FSH or a combination of these hormones did not affect the progesterone production, whatever the stage of diapause. DHA and androstenedione secretion increased in the two last stages of blastocyst growth and was enhanced by LH. The conversion of androstenedione and testosterone into oestrone and oestradiol was observed at all stages of embryonic diapause, indicating that corpora lutea contain aromatase activity even at an early stage. The secretion of oestrone was higher than that of oestradiol. The non-luteal tissue contributed up to 50% of the steroid production; while progesterone and androgen production remained constant, that of oestradiol decreased at the end of the delay period. These results indicated a change in the size and the secretory capacity of the luteal cell related to blastocyst development and implantation. Although progesterone was the main product of the corpora lutea, androgens and oestrogens were also secreted.

Androgens↗
PubMed1989

Pathologic aspects of the umbilical cord after percutaneous umbilical blood sampling.

Percutaneous umbilical blood sampling (cordocentesis) appears to be a valuable new procedure for prenatal diagnosis. In order to evaluate whether focal injury of the umbilical vessels caused by the needle puncture is potentially harmful, we completely examined 50 umbilical cords collected between 1 hour and 20 weeks after cordocentesis. Macroscopic evidence of the needle entry was found in 37 cases, including one giant hematoma of the cord. Within 48 hours after the procedure, microscopic examination of transverse sections taken at the puncture site revealed distinct perforation of the vessel wall, associated in four cases with a small hematoma encircling the vessel. One week after cordocentesis, the vessel wall was partially reformed. There were no histologic differences between needle entry in a vein or in an artery. No thromboses of the umbilical vessels were found.

Blood Specimen Collection↗
PubMed1988

Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.

Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.

Adult↗
PubMed1988

The construction and characterization of a biologically active recombinant IL-2 containing a lysine-rich C-terminal extension.

A polylysine extended gibbon IL-2 (IL-2-L) was constructed by the addition of a lysine-rich oligopeptide, Gly3-(Lys-Lys-Asp)3-Leu-Glu to the C terminus of gibbon IL-2 by using rDNA technology. The bioactivity of the hybrid molecule was comparable to that of normal human rIL-2 in assays measuring T cell proliferation, and in generation of lymphokine-activated killer cells from PBL. Furthermore, the addition of the lysine-rich segment made the molecule more amenable to the chemical derivatization of amino groups. After biotinylation, IL-2-L retained a greater proportion of its bioactivity than normal rIL-2. In addition, biotinylated IL-2-L was capable of simultaneously binding to cell surface IL-2R and streptavidin. Thus, the addition of the lysine-rich oligopeptide facilitated the generation of an active form of biotinylated IL-2 which acts as a bridge between IL-2R-positive cells and avidin-coupled reagents and affinity supports. Such a selective means of labeling and binding IL-2-responsive cells may have great practical utility for IL-2-based immunotherapy.

Amino Acid Sequence↗
PubMed1988

[Epidemiology of chronic renal insufficiency treated by dialysis in a region in France. Changes in a 12-year period].

Between January 1976 and December 1987, 278 patients (172 men, 106 women) aged over 15 and living in a region of some 400,000 inhabitants were treated with dialysis for end-stage chronic renal failure (CRF). The annual incidence of new cases treated was evaluated separately for 3 consecutive 4-year periods: 1976-79 (period A), 1980-83 (period B) and 1984-87 (period C). The incidence rose from 4.6-4.9 in periods A and B to 7.8/100,000 in period C, i.e. a 38 per cent progression. At the start of dialysis the mean age of women did not significantly vary throughout the 3 periods, whereas it increased significantly in men during period C. There was a significant increase of primary glomerulonephritis (GN) throughout the 3 periods: 1.25, 1.70 and 2.35/100,000 respectively; this disease accounted for 27.3, 34.6 and 30.6 per cent of all causes of CRF. Similarly, the incidence of secondary nephropathy (diabetes, amyloidosis) treated with dialysis increased from 0.6 (A) to 1.0 (B) and 1.9/100,000 (C) (P less than 0.05 with period A). The same happened with polycystic kidney: 0.25, 0.65 and 0.93/100,000. During period C, when 95 per cent of primary GN were diagnosed histologically, igAGN (13 per cent), diabetes (13 per cent) and polycystic kidney (12 per cent) were the main causes of CRF. During the whole 12-year period under study, when 80 per cent of primary GN were diagnosed, the prevalence of causes of CRF varied according to the patients' age. In patients under 65 at the start of dialysis primary GN were the principal causes of CRF (36.8 per cent, including 15.5 per cent of IgAGN), followed by secondary nephropathies (20.3 per cent, including 10.7 per cent of diabetes), chronic interstitial nephropathies (18.7 per cent, including 9.6 per cent of reflux nephropathy), hereditary nephropathies (14.4 per cent, including 10.7 per cent of cystic kidney) and vascular nephropathies (7 per cent). Above the age of 65, the principal causes of CRF were chronic interstitial nephropathies (27.7 per cent, including 8.9 per cent of drug-induced nephropathy), followed by secondary nephropathies (20 per cent, including 6.7 per cent of amyloidosis and 11.1 per cent of diabetes), vascular nephropathies (20 per cent), primary GN (12.2 per cent), and hereditary nephropathies (12.2 per cent) including 11.1 per cent of polycystic kidney).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

[Epidemiology of glomerular diseases in a region in France. Changes as a function of periods and the age of patients].

Between January 1, 1976 and December 31, 1987, a histological diagnosis of primary glomerular disease was made in 420 patients born and living at the time of diagnosis in a region of France with some 400,000 inhabitants. The prevalence of glomerular disease during that span of time was 1 in 1,000. The annual incidence of the disease was evaluated separately for 3 consecutive 4-year periods: period A (1976-79), period B (1980-83) and period C (1984-87). Within each of these 3 periods the number of patients with primary glomerular disease was 138, 148 and 115 respectively, and the figures for annual incidence were 8.6, 9.2 and 7.2 respectively in 100,000. Idiopathic IgA glomerulonephritis was the most common of primary glomerular diseases (34.2 per cent), and its annual incidence remained the same throughout the 3 periods: 2.6, 3.2 and 2.8 in 100,000. The incidence of membranoproliferative glomerulonephritis (7 per cent) decreased from 1980 onward (1.2, 0.5 and 0.3 in 100,000) while that of idiopathic proliferative glomerulonephritis (GNPI) with crescents slightly increased (0.25, 0.7 and 0.5 in 100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was significantly less frequent in period C, whereas secondary membranous glomerulonephritis progressed. There was no significant difference between the 3 periods as regards the incidence of other primary glomerular diseases. All histological types of the primary diseases became more frequent in elderly people. Thus, the overall frequency of primary glomerular diseases decreased slightly during the last 4 years, but it increased in the population aged over 65 and diminished in the younger population.

Adult↗