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Biomedical subjects

M Uzan

Publications and source records attributed to M Uzan.

At least 127 records · Page 7Linked to original sources

A nuclease that cuts specifically in the ribosome binding site of some T4 mRNAs.

We have identified a nucleolytic activity in Escherichia coli infected by bacteriophage T4 that introduces cuts in the ribosome binding site of at least two T4 mRNAs. Cutting takes place specifically in the GGAG sequences that are complementary to the 3' end of 16S rRNA (Shine-Dalgarno sequence). The nature of this nucleolytic cut has been investigated by reverse transcriptase mapping, anti-mRNA mapping, utilization of the vaccinia virus guanylyltransferase, and labeling by polynucleotide kinase. We have compared the sequences of target mRNAs with an mRNA of similar sequence but that is not a substrate for the nuclease. This allowed us to narrow down the possibilities for sequence elements that determine nuclease recognition. We hypothesize that this nuclease plays a physiological role in the inhibition of expression of a class of phage proteins.

Base Sequence↗

Influence of haemodialysis membranes on beta 2-microglobulin kinetics: in vivo and in vitro studies.

Amyloidosis of the beta 2-microglobulin (beta 2M) type is a recently recognised complication of dialysis. We studied plasma and ultrafiltrate beta 2M in 36 chronic haemodialysis patients. Long-term dialysis with standard cuprophan membrane in non-oliguric patients and with the AN69 polyacrylonitrile membrane in oliguric patients resulted in lower plasma beta 2M concentrations (means +/- SD, 24.4 +/- 6.6 and 33.0 +/- 8.2 micrograms/ml, respectively) than with cuprophan in oliguric patients (47.0 +/- 13.2 micrograms/ml, P less than 0.01). In acute studies, plasma beta 2M (corrected for haemo-concentration) increased, although not significantly, during cuprophan dialysis (n = 10) from 40.6 +/- 12.2 to 44.8 +/- 7.6 micrograms/ml and decreased during AN69 dialysis (n = 10) from 39.4 +/- 18.0 to 24.3 +/- 7.1 micrograms/ml (P less than 0.02). After 15 min ultrafiltration, beta 2M sieving coefficient in vivo was 0.33 for AN69 but near zero for cuprophan. Total mass transfer of beta 2M across the AN69 membrane during a 4-h dialysis was 142 +/- 45.8 mg (n = 7). AN69, but not cuprophan, membrane fragments incubated in vitro with normal or uraemic plasma exhibited avid [125-I] beta 2M binding (respectively 12.9% vs 0.47% and 6.09% vs 0.06% of total beta 2M bound at 30 min, n = 6, P less than 0.001 for both). No in vitro generation of beta 2M from whole normal or uraemic blood could be demonstrated during incubation with either membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Renal disease associated with heroin abuse].

Thirteen patients developed a renal disease after using heroin alone or in combination with other drugs, for a period of 3 to 12 years. Eleven were IV drug addicts, 2 were sniffers. Six patients had acute tubular necrosis, due to rhabdomyolysis in 5 and to prolonged gentamicin therapy for bacterial endocarditis in 1. Five patients manifested a nephrotic syndrome, and renal biopsy showed various types of glomerulonephritis (GN) without glomerular sclerosis. The two last patients had hypertension with intrarenal vascular lesions and HBsAg was present in their serum. Chronic hemodialysis and/or renal transplantation were required in 2 cases with GN; all other patients recovered normal serum creatinine. There was no specific pathologic picture of heroin abuse in this series.

Adult↗

[Measurement of maternal plasma volume during pregnancy].

An increased maternal plasma volume (PV) is a characteristic phenomenon of normal pregnancy, which may be related to a physiological decrease of peripheral resistances. The authors have studied the plasma volume of 1,105 patients distributed as follows: normal (387), permanently hypertensive patients (84), hypertensive patients during pregnancy (390), patients with apparently isolated RCIU (154) or with a pathological past-history during previous pregnancies (90). It appears that the PV is a sign of a severe HBP, and presents a rather early and good predictive value regarding the weight of the fetus and some complications such as severe UCIU and fetal death in utero. In case of pathological past events or pre-existing hypertension, the PV enables to differentiate rather well patients who will be prone to a complicated pregnancy. In view of these results, utilization and interpretation criteria of this parameter during pregnancies with hypertension or pregnancies in which there is a suspicion or a risk of intra-uterine growth delay, are defined.

Adult↗

The prevalence of chondrocalcinosis in the human knee joint. An autopsy survey.

The prevalence of pathological calcifications in the menisci and articular cartilage of both knees was investigated macroscopically and radiologically in 130 consecutive autopsies. The mean age of the subjects was 72 +/- 13 years. Only 8 subjects were less than 50 years old. All had been admitted to hospital and no patient had a history of joint disorders. Half of the patients were male. Calcifications were found in 27 (20.7%) cases, all over 60 years of age. There were 15.4% males and 26.1% females affected. The incidence of intraarticular calcifications in females increased from 11.1-37.5% and in males from 20-29.4% for the 60-69 year age group and the over 80-year age group, respectively. One third of affected cases had only meniscal and 2/3 had both meniscal and chondral calcifications. Isolated meniscal calcifications were found more often in 1 and mixed meniscal and chondral calcifications were found in both knees. Severe destructive articular cartilage lesions were observed significantly more often in joints with intraarticular calcifications than in joints of age matched subjects without calcifications. Joints with calcifications showed little evidence of synovial inflammation. Similarly, no specific relationship was found between the presence of crystal and amyloid deposits in the knees examined.

Aged↗

Covalent linkage of the synthetic adjuvant MDP to the synthetic polypeptide (T,G)-A-L changes the specificity of the immune response at the T and B cell level.

It is now well established that the synthetic molecule MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) can be a good adjuvant of immunity when covalently linked to antigen. The question raised in this work is whether conjugation of antigen to the immunomodulatory molecule MDP can modify the specificity of the antibodies and T cells induced following immunization. Using the well characterized synthetic polypeptide antigen, poly(L-Tyr,L-Glu)-poly(DL-Ala)--poly(L-Lys) [(T,G)-A--L], we show that immunization of C57B1/6 (H-2b) mice with MDP-(T,G)-A--L conjugate elicits at least two types of antibody directed against the poly(DL-Ala)--poly(L-Lys) (A--L) part of the antigen, and against new determinant(s) formed by MDP and a portion of the (T,G)-A--L molecule. Interestingly, the poly-(L-Try L-Glu) side chains thought to constitute the major antigenic determinants of the (T,G)-A--L molecule were not recognized. Lymph node cells from (T,G)-A--L immunized mice can be equally well stimulated in vitro by (T,G)-A--L or by MDP-(T,G)-A--L, whereas lymph node cells from MDP-(T,G)-A--L primed animals can be stimulated only when challenged by the conjugate used for immunization, and not by the free synthetic polypeptide (T,G)-A--L. The data presented here show that the coupling of a low mol. wt molecule such as MDP (mol. wt approx. 500) to an antigen can greatly modify the immune response directed against this antigen. Furthermore, (1) different antibody specificities are elicited depending upon whether the priming is done with free MDP and antigen or with MDP covalently linked to the antigen; (2) although still accessible on the conjugate, an epitope which represents the major antigenic determinant on the free polypeptide appears to be silent when presented on the conjugate; and (3) new determinant(s) formed by the chemical linkage of the polypeptide to the synthetic adjuvant are involved in the priming of T cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

Treatment of polyhydramnios with prostaglandin synthetase inhibitor (indomethacin).

Polyhydramnios, which is caused by an excess of amniotic fluid, was diagnosed uniformly in eight patients by ultrasound examination and clinical symptoms, namely, premature uterine contraction, abdominal pain, and respiratory discomfort that resulted from excessive pressure on the diaphragm. Fetal anomalies incompatible with extrauterine existence were excluded by serum alpha-fetoprotein levels, repeated sonography, amniocentesis, and chromosomal analyses. Patients were treated with 2.2 to 3.0 mg of indomethacin/kg body weight/day. The treatment was started at an average gestational age of 24 +/- 0.5 weeks and continued for 2 to 11 weeks. All patients had significant improvement with a simultaneous reduction in amniotic fluid volume, fundal height, and umbilical perimeter. All patients were delivered satisfactorily at an average of 39 weeks' gestation. The fetuses were within the normal body weight range of 2750 to 3600 gm and showed normal development during the neonatal period of 2 to 6 months. Before delivery without indomethacin, the polyhydramnios reformed. Adverse effects or intolerance to the drug was avoided by either a reduction in the dose or cessation of indomethacin therapy. Our studies suggest that indomethacin therapy is an effective way to manage pregnancy complicated by polyhydramnios.

Adult↗

[The Doppler in obstetrics: experience of the Baudelocque Clinic].

The authors report three years of experience with the use of the Doppler in Obstetrics. Certain notions may be integrated to the principles of clinical decision. The diastolic index D at the umbilical artery increases regularly during a normal pregnancy. It is significantly decreased in case of intra-uterine growth delay (IUGD). When this index reaches zero, it may be considered as a reliable criteria for fetal extraction. Certain notions must be verified: the index seems frequently altered in case of chromosomal abnormality. Some results still depend on research. The index measured at the uterine arteries could predict IUGD and at the level of the fetus' internal carotids, its elevation could be one of the first signs of fetal hypoxia. Finally, the index was measured during normal labor. In case of deceleration it is markedly altered. Thus, this could be an additional element of fetal monitoring.

Blood Volume↗

[Improvement in the prenatal etiologic diagnosis of severe 2d trimester oligo-amnios by intra-amniotic injection of physiologic solution].

In reference to 4 severe cases of oligo-amnios of the second trimester of pregnancy, the authors advocate a method in order to improve the pre-natal diagnosis by intra-amniotic injection of a normal saline solution. This method facilitates the morphological exploration of the fetus by sonogram and enables to obtain a fetal karyotype by umbilical or amniotic tap. The potential risk of this technique are described.

Amniocentesis↗

[Fetal diastolic index in the internal carotid arteries. Preliminary results in normal and pathologic pregnancies].

The authors studied a series of 87 blood flow measurements in the internal carotid arteries of fetuses. After a brief survey of cerebral blood flow a description is given of the technique for measuring this flow. They use the index D/S just as in measuring umbilical artery flow. In normal pregnancy the carotid diastolic index hardly rises and stays low, which confirms that there is a high resistance in the system. When abnormal flow rates are found in the umbilical artery the carotid diastolic index rises to protect the brain against hypoxia. The rise in the carotid diastolic index could be the last abnormality which precedes the appearance of fetal cardiac rhythm changes.

Blood Flow Velocity↗

[Results of autopsy examination of knee cartilage in 120 patients dying in the hospital. I. Femoro-patellar joint].

The authors have performed the pathological examination of the knees of 57 women and 63 men or 112 patients over the age of 50, who died in the hospital. The lesions of the patellar and trochlear cartilages were studied and classified according to four categories: stage I: non extended fissures; stage II: fissures extending over 25 p. cent of the articular surface; stage III: fissures associated with small deep ulcerations of the cartilage; stage IV: deeps and extended ulcerations of the articular cartilage exposing the sub-chondral bone. Cartilage alterations were found in 93.3 p. cent of the patellas; 26.2 p. cent of stage I; 22.5 p. cent of stage II, 27.1 p. cent of stage III; 17.5 p. cent of stage IV. These alterations are bilateral and symmetrical, most of the time. Their frequency and severity increase with age. Thus, deep and extended ulcerations (stage IV) of the patellar cartilage have a frequency of 1.9 p. cent before the age of 60.8 p. cent between 60 and 70 years, 13.6 p. cent between 70 and 80 years and 38.9 p. cent after 80 years. Alterations of the patellar cartilage are more frequent and more severe in women than in men. In 85.7 of the patellas they occupy both facets, overriding the patellar crest; more seldom, they are exclusively localized to the medial patellar facet (11.6 p. cent) or lateral facet (3.1 p. cent). Alterations of the trochlear cartilage, although more common are less frequent than that of the patellar cartilages. Patellar osteophytosis is very frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The T4 mot protein functions as part of a pre-replicative DNA-protein complex.

Middle-mode RNA synthesis in T4-infected cells takes place before replication of phage DNA commences. What distinguishes it from early-mode RNA synthesis is that initiation of middle RNA depends on T4-coded proteins, in particular on the mot gene product. mot protein is localized in a DNA-protein complex which forms during the first few minutes of infection. All of the cell's mot protein is bound in this complex, and it continues to be bound long after the synthesis of mot protein has stopped. When we infect Escherichia coli with T4 carrying a temperature-sensitive mutation in the mot gene, we find a correlation between the physiology of this mot mutant and the amount of mot protein bound in the DNA-protein complex. Although there is some host RNA polymerase in the complex, mot protein does not seem to bind to this enzyme. Two other T4-coded proteins, of molecular weights 17,600 and 15,000, are also found in the pre-replicative DNA-protein complex. One of these, p17,600, is coded for by a 750-base pair region located between genes 39 and 56; p17,600 appears to be the recently described motB gene product. The other protein, p15,000, is not an RNA polymerase-binding protein; it is characterized by its strong binding to the DNA-protein complex.

DNA Replication↗

Carpal tunnel syndrome, shoulder pain and amyloid deposits in long-term haemodialysis patients.

Carpal Tunnel Syndrome (CTS), and Shoulder Pain and Stiffness (SPS) are common in very long-term haemodialysis patients. To know whether this is a fortuitous association or if there is a link between these two manifestations a retrospective analysis of clinical charts, CTS surgical reports, tendon and synovia biopsies (Congo red, Crystal violet and Thioflavin T) was undertaken for 110 patients treated by haemodialysis (HD) for eight years or more. SPS was less frequent (24%) in 58 patients not operated on for CTS than in 52 operated patients (SPS incidence: 77%). Furthermore the 38 patients with amyloid deposits at carpal biopsy had a very significantly (p less than 0.001) higher incidence of SPS (95%) than the 14 operated patients free of amyloid deposits (SPS incidence: 28%). Hence, amyloid deposits represent a pathological link between these two correlated manifestations in very long-term haemodialysis patients.

Amyloidosis↗

Influence of the oral administration of micronized progesterone on plasma and tissue levels of steroids in human pregnancy.

A single dose of micronized progesterone, orally administered to women at different stages of pregnancy, induced an immediate increase in the plasma levels of progesterone. Progesterone was administered to another group of women just before elective cesarean section. Levels of progesterone, oestradiol-17 beta and oestrone were determined in plasma, placenta and at different sites of the myometrium obtained during the surgical procedure. Results were compared to those observed in a control group of women who did not receive progesterone. Progesterone levels demonstrated a marked increase in plasma and in the whole myometrium 150 min after administration; the levels then decreased rapidly to control values within one hour. The concentrations of progesterone in the placenta did not show any change. Evident modifications of the oestrogen levels appeared in the myometrium and in the placenta after the administration of progesterone whereas no change occurred in the plasma. No difference was observed in estradiol-17 beta in the myometrium whereas an increase was seen in the placenta. Estrone levels decreased in the myometrium and in the placenta. This study demonstrates a prompt delivery of an orally administered natural progesterone to the myometrial target tissue and subsequent modifications in the estrogen pattern. This provides a theoretical mechanism for the clinical use of progesterone in the prevention of premature labor.

Administration, Oral↗

Oral administration of micronized natural progesterone in late human pregnancy. Effects on progesterone and estrogen concentrations in the plasma, placenta, and myometrium.

A single dose of micronized oral progesterone was administered to 15 pregnant women immediately prior to elective cesarean section. Levels of progesterone, 17 beta-estradiol, and estrone were measured in the plasma, in the placenta, and at different sites in myometrium obtained during the surgical procedure. Results were compared to those observed in a control group of women who did not receive progesterone. Progesterone levels demonstrated a marked increase in plasma and in the whole myometrium 150 minutes after administration. The levels then decreased rapidly to control values in 1 hour. The concentrations of progesterone in the placenta did not show any changes. No difference appeared in 17 beta-estradiol levels in the plasma or the myometrium, whereas an increase was observed in the placenta. Estrone levels did not change in the plasma, but they decreased in the myometrium and in the placenta.

Administration, Oral↗