Biomedical subjects

L Harel

Publications and source records attributed to L Harel.

At least 55 records · Page 3Linked to original sources

PubMed1996

Comparative evaluation of cefixime versus amoxicillin-clavulanate following ceftriaxone therapy of pneumonia.

Preliminary results have recently shown that an early switch from parenteral antimicrobials to an oral substitute provides an effective means of treating pneumonia in pediatric patients. In a controlled randomized study, 62 children with community-acquired lobar/segmental pneumonia were selected to receive 8 days of cefixime or amoxicillin-clavulanate after an initial therapy of two doses of parenteral ceftriaxone. Enrollment criteria included: age 6 months to 5 years, fever > 38.5 degrees C, white blood cell (WBC) count > or = 15,000/ mm3, and lobar/segmental pneumonia on chest radiograph. Twenty-nine patients were randomized to receive oral cefixime and 33 to oral amoxicillin-clavulanate. The two groups were comparable in the following pretreatment parameters: age, duration of illness, temperature, mean WBC count, erythrocyte sedimentation rate, C-reactive protein, and need for hospitalization. Days of resolution of high fever, tachypnea, cough, grunting, and laboratory test abnormalities were similar in the two groups. Clinical response at the end of treatment showed cure, improvement, and failure in 97%, 3%, and 0%, respectively, in the cefixime group and in 88%, 6%, and 6%, respectively in the amoxicillin-clavulanate group (P = NS). We conclude that young children with community-acquired lobar/segmental pneumonia can be successfully treated with 2 days of parenteral ceftriaxone followed by 8 days of oral cefixime or amoxicillin-clavulanate.

Administration, Oral↗

PubMed1996

Serum-sickness-like reaction associated with minocycline therapy in adolescents.

OBJECTIVE: To describe a serum-sickness-like reaction in five adolescents treated with minocycline. CASE SUMMARY: Five adolescents developed a rash and arthralgias/arthritis after taking minocycline for 10-30 days. Symptoms resolved gradually after the medication was stopped. DISCUSSION: Serum sickness is not described in the pharmacology literature as an adverse effect of minocycline, and in the English literature there are only two case reports. The migration inhibitory factor assay and mast cell degranulation test were positive in four of the five patients. The results of these assays were consistent with a role for minocycline in causing these reactions. CONCLUSIONS: Clinicians should be aware of the possibility of serum-sickness-like reaction as an adverse effect of minocycline.

Adolescent↗

PubMed1996

Recombinant human insulin-like growth factor (IGF) binding protein-3 stimulates prostate carcinoma cell proliferation via an IGF-dependent mechanism. Role of serine proteases.

Insulin-like growth factor-binding proteins (IGFBPs) modulate IGF action at cellular level, through either inhibition or potentiation, and they also have intrinsic activity that is independent of their binding to IGFs. In prostate carcinoma (PC-3) cells, which are capable of growth for several days in serum-free medium, non-glycosylated recombinant human IGFBP-3 (rhIGFBP-3) had a biphasic mitogenic effect, stimulation being dose-dependent up to 20 ng/ml, followed by progressive depression down to zero stimulation at 150-200 ng/ml. This mitogenic effect was not intrinsic activity, but involved IGF-II secreted by the cells, since stimulation was abolished in the presence of anti-type 1 IGF receptor antibody (alpha IR-3). Western ligand- and immunoblot analysis of the culture media revealed several IGFBP species, in particular IGFBP-3 which exhibited an electrophoretic profile characteristic of limited proteolysis. The amounts of the proteolytic fragments increased in parallel with the concentrations of added rhIGFBP-3, but a large amount of intact protein remained at the highest concentrations added. When a serine protease inhibitor, 4-(2-aminoethyl)-benzenesulphonyl fluoride (Pefabloc SC), was added at concentrations demonstrated to be non-toxic to the cells, IGFBP-3 proteolysis was diminished and rhIGFBP-3-induced stimulation of proliferation was suppressed. Conversely, in the presence of plasminogen transformed to plasmin by urokinase secreted by the cells, proliferation stimulated by rhIGFBP-3 and its proteolysis were enhanced. Our results suggest that the biphasic mitogenic effect of rhIGFBP-3 on PC-3 cells reflects changes in the availability to the cells of the IGF-II they secrete. This availability depends on the extent of IGFBP-3 proteolysis (which promotes release of bound IGF-II) and on the proportion of intact forms (which sequestrate secreted IGF-II).

Adenocarcinoma↗

PubMed1995

Great grand multiparity--beyond the 10th delivery.

OBJECTIVE: To investigate the perinatal outcome and obstetric complications of women delivering for the 10th time or more. METHODS: Four hundred twenty women of great grand multiparity were analyzed in a modern health care setting and compared with our general population of obstetric patients, with regard to past history, maternal age, gestational age, mode of delivery, fetal outcome and intercurrent medical/obstetric problems. RESULTS: The study group showed significantly lower rates of low birth weight infants and instrumental delivery. No significant difference was seen in the incidence of cesarean section, pathologic fetal presentation, maternal hypertension, gestational diabetes, hemorrhage, or perinatal morbidity or mortality. There was a slightly higher incidence of twin births compared with the general population. CONCLUSION: It is probable that women capable of reaching their 10th delivery are basically healthy. If offered adequate perinatal care, they are not a high-risk group during subsequent deliveries.

Adult↗

PubMed1995

The grand multipara.

Grandmultiparity (GMP) has long been considered an obstetric complication for both mother and fetus, although recent studies indicate that, with proper perinatal care, women with high-parity rates are no longer at high risk. The current study examines the outcome of delivery in 1700 women in their fifth or more delivery, as compared with two control groups: 622 primiparas and 735 multiparas (two to three previous deliveries). Excellent prenatal care was available free of charge to all parturients. Our objectives were to evaluate the management of GMP in contemporary obstetrics and to assess whether grand multiparas are still high-risk patients. The age of the grandmultiparas was significantly higher compared with with the control groups, which may explain the higher incidence among them of antenatal medical disorders, such as diabetes mellitus and hypertensive disease. No significant differences were found among the three groups for preterm or post-term births, small-for-gestational-age infants, polyhydramnios, oligohydramnios, perinatal death, fetal distress, multiple births, placenta previa, abruptio placentae or cord prolapse. Macrosomia was markedly higher in the grandmultiparas and multiparas than in nulliparas. Thus, our results indicate that good perinatal care can ensure better results in grandmultiparas, and that grandmultiparity no longer needs to be considered a high-risk obstetric category in our population.

Adult↗

PubMed1995

Normal diurnal variation in serum cortisol concentration in asthmatic children treated with inhaled budesonide.

BACKGROUND: Twenty-four-hour serum cortisol secretion is a sensitive parameter for the assessment of the pituitary-adrenal function of asthmatic children treated with inhaled corticosteroids. This study was undertaken to determine the effect of the long-term administration of inhaled budesonide on 24-hour cortisol production in young children with asthma. METHODS: We studied 11 children, aged 7 to 12 years, with severe perennial asthma. All had been receiving 100 micrograms of inhaled budesonide twice daily, administered with a spacer device, for 3 to 5 years. Serum cortisol concentration was measured at 8:00 A.M., 60 minutes after intravenous administration of 0.25 mg of corticotropin, and every 30 minutes for 24 hours in an open-design study. Urinary cortisol secretion was measured by 24-hour urine collection. All determinations were made with a radioimmunoassay kit. RESULTS: The individual morning serum cortisol concentration and the serum cortisol concentration at 60 minutes after corticotropin stimulation were within normal limits in all children. The 24-hour urinary cortisol excretion was also normal. The individual 24-hour serum cortisol concentration showed a normal pattern in all children, with no evidence of nocturnal suppression of serum cortisol concentration. CONCLUSION: Prolonged (3 to 5 years) administration of 200 micrograms/day of inhaled budesonide in young children with severe asthma does not impair pituitary-adrenal function, even according to the sensitive test for 24-hour serum cortisol secretion.

Administration, Inhalation↗

PubMed1995

The treatment of rheumatic carditis: a review and meta-analysis.

We performed a meta-analysis of the literature on the treatment of established rheumatic carditis to determine if corticosteroid therapy is superior to salicylates in preventing the sequela of inflammation--valvular damage. We identified 22 reports of comparative trials published since the introduction of corticosteroids in 1949. Five of the 22 studies met the criteria we established for the meta-analysis, which included using randomization and a 1-year follow-up for the presence of a new pathologic apical systolic murmur. Based on the meta-analysis, the advantage of corticosteroid treatment over salicylates in preventing a pathologic murmur at 1 year posttreatment is not statistically significant (estimated odds ratio 0.88; 95% confidence interval: 0.53 to 1.46). However, the meta-analysis is dominated by 1 large negative trial, and there was significant heterogeneity in the results obtained from the studies in the meta-analysis; thus, the question of whether corticosteroid therapy is marginally superior to salicylates for the prevention of valvular heart disease from rheumatic fever remains open.

Adrenal Cortex Hormones↗

PubMed1995

Arthritis after mumps and measles vaccination.

Measles, mumps, and rubella vaccine carries a risk of joint symptoms particularly in children under 5 years. A boy who presented with an inflamed knee after measles and mumps vaccination is reported; synovial fluid aspirated from the joint contained 4.3 x 10(9)/l leucocytes. It is thought that the mumps component is the aetiological cause of acute monoarthritis.

Acute Disease↗

PubMed1994

Density-dependent inhibition of mouse embryo fibroblast growth: involvement of IGFBP-3.

Up until now the phenomenon of density dependent inhibition of growth has remained unexplained; one hypothesis suggests that autocrine growth inhibitory molecules are secreted in the medium of dense cultures and inhibit cell growth. From medium conditioned by mouse fibroblasts we purified a 45-kDa inhibitory factor which is an insulin-like growth factor binding protein (IGFBP-3). Based on different results we assumed that IGFBP-3 is a bifunctional molecule and has inhibitory function independent of its known function of binding IGF. In the present publication we attempted to verify whether IGFBP-3 is involved in DDI of growth. IGFBP-3 was secreted by mouse embryo fibroblasts (MEF). Its concentration in the medium increased with the cell density of the culture and was large at saturation density when DNA synthesis was minimum. Medium conditioned (CM) by dense culture was inhibitory compared to fresh medium and this inhibition disappeared when CM was preincubated with anti-IGFBP-3 IgG. Addition of FGFb to MEF dense cultures increased but transiently DNA synthesis which decreased as soon as 24 h after growth factor addition. By contrast accumulation of IGFBP-3 in the medium increased with time and was large at the time when DNA synthesis was minimum. Our results suggest that the rapid decrease of DNA synthesis in stimulated dense culture was the result of both depletion of the medium (particularly of FGFb) and the increase in concentration of inhibitory molecules like IGFBP-3. Addition of FGFb and preincubation of CM with anti-IGFBP-3 IgG were able to greatly reduce the inhibition.

Animals↗

PubMed1994

Difference in biological effects between insulin-like growth factor binding protein 1 and 3.

Insulin-like growth factor binding proteins 1 and 3 are essentially known as regulators of IGF bioactivity. However, we previously showed that IGFBP-3 was able, in chick embryo fibroblast (CEF), to 100% inhibit DNA synthesis stimulated by calf serum, while the maximal inhibition found with IGFBP-1 was 60%, suggesting a difference between the two IGFBPs in their biological functions. Results of the present work agree with this assumption: (a) Recombinant human IGFBP-3, like rat IGFBP-3, was able to 100% inhibit DNA synthesis stimulation induced by human serum, while this stimulation was 75% decreased by IGFBP-1. However, the most striking difference was observed when the effects of the two IGFBPs were compared for stimulation induced by a serum growth factor (SGF) fraction depleted in IGFs. Stimulation induced by the SFG fraction was more significantly decreased (p < 0.001) by IGFBP-3 than by IGFBP-1. The mean percent inhibition +/- SEM was 67.1 +/- 2.5 in the presence of IGFBP-3 (200 ng/ml) and 29.3 +/- 2.7 and 34.2 +/- 4 in the presence of 200 and 400 ng/ml IGFBP-1 respectively. Inhibition by 200 ng/ml IGFBP-1 and inhibition by 6 ng/ml IGFBP-3 were additive. However, inhibition by IGFBP-3 and that by IGFBP-1 were no longer additive at high concentrations of IGFBP-3, which might thus replace IGFBP-1. (b) FGF stimulation of CEF was similarly inhibition (65% and 70%) by IGFBP-1 and IGFBP-3. (c) TGF beta stimulation of CEF was more strongly decreased by IGFBP-3 (90%) than by IGFB-1 (60%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of methotrexate on radiologic progression in juvenile rheumatoid arthritis.

OBJECTIVE: To assess the effects of methotrexate (MTX) therapy on radiologic progression in juvenile rheumatoid arthritis (JRA). METHODS: We evaluated serial wrist radiographs for carpal length in 23 JRA patients with bilateral wrist involvement, before and during MTX treatment. These carpal length measurements were compared with established norms for carpal length in a healthy pediatric population. RESULTS: Both clinical responders to MTX (17 of 23 patients) and nonresponders (6 of 23) had decreasing carpal length prior to initiation of the treatment. Eleven of the 17 clinical responders had improved carpal length after a mean of 2.5 years of MTX treatment. All 6 clinical nonresponders had progressive loss of carpal length. CONCLUSION: MTX treatment resulted in radiologic improvement, as measured by carpal length, in the majority of children with JRA who had a clinical response to MTX.

Arthritis, Juvenile↗

PubMed1993

Endometrial suction in luteal phase as a method of late postcoital contraception.

In a pilot study group of 25 women presenting in our clinic after exposure at ovulation to undesired pregnancy, endometrial suction by means of a Pipelle catheter was performed. Sixteen of the 25 women had proven fertility and 9 had never tried to conceive. The women were aged 18 to 38 years. Pathological dating of endometrial sampling verified that the patients were actually post-ovulation in all cases studied. hCG tests were performed 10 to 14 days after endometrial suction and all were negative. We conclude that endometrial suction in the luteal phase is a possible means of postcoital non-hormonal contraception, and we are currently expanding our study.

Adolescent↗

PubMed1993

IGF binding protein-3 secreted by the prostate adenocarcinoma cells (PC-3): differential effect on PC-3 and normal prostate cell growth.

Deregulation of growth in malignant cells has been suggested to be the result of increased secretion by these cells, of autocrine growth factors; alternatively, this deregulation has been assumed to be related to loss of sensitivity by malignant cells to secreted inhibitory molecules. The results of the present publication lend new support to both hypotheses. We recently showed that human prostate adenocarcinoma cells (PC-3 cells) secreted insulin-like growth factor binding proteins (IGFBP) of 45, 34 and 25 kDa. From medium conditioned by dense cultures of PC-3 cells, we have now purified two IGFBPs of M(r) 45 kDa and 34 kDa. The N-amino terminal sequences were determined, and it was shown that they are IGFBP-3. IGFBP-34 appeared to be a deglycosylated form of IGFBP-45. The two IGFBPs had more affinity for IGF-II than for IGF-I. IGFBP-45 and IGFBP-34 were growth-inhibitory factors of chick embryo fibroblasts (CEF): they totally inhibited DNA synthesis stimulated by serum in CEF. Our results point to a clear difference between the effects of these IGFBPs upon growth of normal prostate cells and malignant PC-3 cells. At a concentration of 150 ng/ml, they inhibited growth of normal prostate cells even in the presence of 1 microgram/ml insulin. This suggests that such inhibition was not simply the result of a decrease by the IGFBP of stimulation induced by serum IGF or IGF secreted by the cells. At a concentration of 150 ng/ml, IGFBP did not modify the growth of PC-3 cells. In contrast, it stimulated growth of PC-3 cells when added at a concentration lower than 50 ng/ml (about 1 nM). Our results thus provide new insight concerning the regulation of growth in PC-3 cells.

Adenocarcinoma↗

PubMed1992

Insulin-like growth factor binding protein (IGFBP-3), an inhibitor of serum growth factors other than IGF-I and -II.

Our results show that an insulin-like growth factor binding protein, IGFBP-3, purified from rat serum, is an inhibitor of chick embryo fibroblast (CEF) growth. It abolished DNA synthesis in CEF stimulated by IGF-I as well as by human serum. Rat IGFBP-3 and IDF45 (an inhibitory diffusible factor secreted by mouse cells) had the same activities, confirming that they have an intrinsic capacity to inhibit serum stimulation and may be considered as growth inhibitors. Our data show that inhibition by IGFBP-3 of serum stimulation was not simply the result of its inhibition of IGF present in the serum: 1) While anti-IGF-I IgG was able to completely inhibit stimulation induced by added IGF-I, it did not decrease stimulation induced by 1% human serum. Anti-IGF-II IgG inhibited the stimulation induced by added IGF-II, but only 25% decreased the stimulation induced by 0.7% serum. The percent inhibition was not significantly increased when the concentration of serum was decreased to 0.2%, which induced 140% stimulation of DNA synthesis; 2) stimulation by 0.2% serum was much more inhibited by IGFBP-3 than by IgG anti IGF-II; 3) after separation of IGF-I and IGF-II from serum by chromatography of acidified serum proteins on BioGel P150, the remaining serum proteins (with a molecular mass greater than 45 kDa) which were depleted in IGF-I and -II (verified by RIA determination) still stimulated DNA synthesis, and this stimulation was 80% inhibited by IGFBP-3.

Animals↗

PubMed1992

Stimulation by TGF beta of chick embryo fibroblasts--inhibition by an IGFBP-3.

The multiple effects of TGF beta on cell proliferation are not well understood. Our results show that TGF beta was a good but transient mitogen for chick embryo fibroblasts. DNA synthesis was three- to fourfold increased, even at high concentrations of TGF beta. We did not show a bimodal effect. An inhibitor of cell growth, that inhibits 100% of stimulation induced by serum in CEF, was purified to homogeneity from medium conditioned by mouse 3T3 cells. This inhibitor has been shown to be an IGF-binding protein (mIGFBP-3). In the present work, this mIGFBP-3 inhibited the TGF beta stimulation by about 50%, while the stimulation induced by PDGF or insulin was not inhibited by mIGFBP-3. Furthermore, TGF beta stimulation, in the presence of a high concentration of insulin in conditions which would saturate IGF receptors, was not significantly inhibited by mIGFBP-3. All together these results suggest that a part of the mitogenic effect of TGF beta may be through increasing IGF secretion and eventually other growth factors such as PDGF (as suggested previously).

3T3 Cells↗

PubMed1992

Synthesis and secretion by mouse 3T3 cells of an inhibitor of cell growth (mIGFBP-3): correlation with cell proliferation.

Our results show that stimulation by serum of dense cultures of 3T3 cells rapidly induced increased synthesis of a growth inhibitor (mIGFBP-3) capable of binding IGF. mIGFBP-3 was secreted by stimulated cells immediately after its synthesis, and accumulated in the medium. Accumulation of mIGFBP-3 in the medium increased, as a function of growth factor (bFGF, PDGF, insulin) concentrations and time. bFGF was the best stimulatory factor for both DNA synthesis and accumulation of mIGFBP-3 in the first 24 h of incubation. DNA synthesis was arrested after 48 h of incubation with bFGF when accumulation of mIGFBP-3 was maximal. Since we showed that mIGFBP-3 is able to inhibit bFGF stimulation of DNA synthesis in mouse fibroblasts, it is possible that the accumulation of mIGFBP-3 induces a feedback regulation of cell growth.

3T3 Cells↗

PubMed1992

Purification from transformed mouse fibroblast of a cell growth inhibitor which is an IGF-binding protein.

From medium conditioned by 3T3 cells, we had previously purified an inhibitory factor of Mr 45 kDa which we termed IDF45 (inhibitory diffusible factor). The protein was able to 100% inhibit stimulation induced in CEF by 1% calf serum and to reversibly prevent cell growth. We then demonstrated that IDF45 was an IGF-binding protein. Our results suggested that IDF45 was a bifunctional molecule able to bind IGF and to inhibit DNA synthesis stimulated by this hormone, but also to inhibit stimulation of DNA synthesis induced by another growth factor in serum. Indeed, its N terminal amino acid sequence has great homology with that of IGFBP-3 and IDF45 is now proposed to be named IGFBP-3 (mouse IGF binding protein). Present results show that Ha-ras transfected 3T3 cells (EJ cells), like 3T3 cells, secrete a mIGFBP-3 molecule. In addition, transfected cells secrete a doublet of an IGF-binding protein (IGFBP-28) of Mr 28 kDa which is not secreted by untransformed 3T3 cells. IGFBP-28 has been purified and characterized in this work. Various results suggest that IGFBP-28 is not a degradation product of mIGFBP-3. Its N terminal amino acid sequence was different from that of mIGFBP-3. IGFBP-28 inhibited DNA synthesis stimulated by IGF-I, but much more IGFBP-28 protein than mIGFBP-3 was required to prevent this stimulation. In agreement with this result, IGFBP-28 has low affinity for IGF-I. In contrast, IGFBP-28 has high affinity for IGF-II. Like mIGFBP-3, IGFBP-28 was able to inhibit the stimulation induced by serum in CEF and to reversibly prevent growth, though with a specific activity lower than that of mIGFBP-3. It has also the capacity to inhibit stimulation of DNA synthesis induced by high molecular weight serum proteins depleted in IGF-I and II. In conclusion we have shown that transformation of 3T3 cells with Ha-ras induced the synthesis of a new IGF binding protein in medium conditioned by normal 3T3 cells. Our results suggest that IGFBP-28 like mIGFBP-3 is a bifunctional protein able to inhibit stimulation induced by IGF and by serum proteins different from IGFs.

3T3 Cells↗

PubMed1991

Presence of IDF45 (mlGFBP-3) binding sites on chick embryo fibroblasts.

IDF45 (inhibitory diffusible factor) a mouse insulin-like growth factor binding protein (mlGFBP-3) has been shown to 100 percent inhibit DNA synthesis stimulated by serum in chick embryo fibroblasts (CEF). Our previous results suggested that this large inhibition by IDF45 of serum stimulation was not just the result of its inhibitory activity toward IGF present in serum. The addition of Mn2+ (10(-3)M) in the incubation medium enables us to show the presence of numerous binding sites per cells (about 60,000) of mlGFBP-3. However the dissociation constant (10(-8)M) indicated that this mouse IGFBP-3 bound to the membrane with low affinity. These findings lend new support to the assumption of the bifunctional property of IGFBP-3, which would have an effect outside the cell (binding of IGF in the medium) and another effect within cells or on the surface.

Animals↗