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G Haddad

Publications and source records attributed to G Haddad.

At least 19 recordsLinked to original sources
PubMed2001

Mediterranean Sea surface radiocarbon reservoir age changes since the last glacial maximum.

Sea surface reservoir ages must be known to establish a common chronological framework for marine, continental, and cryospheric paleoproxies, and are crucial for understanding ocean-continent climatic relationships and the paleoventilation of the ocean. Radiocarbon dates of planktonic foraminifera and tephra contemporaneously deposited over Mediterranean marine and terrestrial regions reveal that the reservoir ages were similar to the modern one (approximately 400 years) during most of the past 18,000 carbon-14 years. However, reservoir ages increased by a factor of 2 at the beginning of the last deglaciation. This is attributed to changes of the North Atlantic thermohaline circulation during the massive ice discharge event Heinrich 1.

Animals↗
PubMed2001

Nucleolar damage correlates with neurotoxicity induced by different platinum drugs.

Platinum-based drugs are very useful in cancer therapy but are associated with neurotoxicity in the clinic. To investigate the mechanism of neurotoxicity, dorsal root ganglia of rats treated with various platinum drugs were studied. Cell body, nuclear and nucleolar dimensions of dorsal root ganglia sensory nerve cells were measured to determine morphological toxicity. Sensory nerve conduction velocity was measured to determine functional toxicity. After a single dose of oxaliplatin (10 mg kg(-1)), no significant change in nuclear and cell body diameter was seen but decreased nucleolar size was apparent within a few hours of treatment. Changes in nucleolar size were maximal at 24 hours, recovered very slowly and showed a non-linear dependence on oxaliplatin dose (r(2)= 0.99). Functional toxicity was delayed in onset until 14 days after a single dose of oxaliplatin but eventually recovered 3 months after treatment. Multiple doses of cisplatin, carboplatin, oxaliplatin, R, R-ormaplatin and S, S-ormaplatin were also associated with time-dependent reduction in nucleolar size. A linear correlation was obtained between the rate of change in nucleolar size during multiple dose treatment with the series of platinum drugs and the time taken for the development of altered sensory nerve conduction velocity (r(2)= 0.86;P< 0.024). Damage to the nucleolus of ganglionic sensory neurons is therefore linked to the neurotoxicity of platinum-based drugs, possibly through mechanisms resulting in the inhibition of rRNA synthesis.

Animals↗
PubMed2001

Prenatal diagnosis and early in utero management of fetal dyshormonogenetic goiter.

We present a case of a fetal dyshormonogenetic goiter diagnosed by ultrasound examination at 24 weeks of gestation, in a woman with no past history of thyroid disease or goitrogen treatment and with normal thyroid tests, including absence of auto-antibodies. In this situation, fetal goiter may only be associated with fetal hypothyroidism, therefore cord blood sampling was not performed but early treatment was initiated. Amniotic fluid instillation of thyroid hormone led to a rapid decrease in amniotic fluid volume and a clear reduction in thyroid goiter. However, fetal thyroid volume did not totally normalise, and cord blood analysis at birth showed elevated fetal TSH level. As prenatal treatment of fetal hypothyroidism remains controversial in euthyroid mothers, the main objective is to prevent obstetrical complications of large goiters. Therefore, in some selected cases with no maternal history of thyroid disease and normal thyroid function tests, cordocentesis is not necessary to confirm fetal thyroid status or to adjust fetal treatment.

Adult↗
PubMed2000

Prenatal ultrasonographic diagnosis of the popliteal pterygium syndrome.

The prenatal ultrasound identification of a cleft lip and palate, equinovarus feet with severe lower limb malposition and genital abnormalities led to the prenatal diagnosis of popliteal pterygium syndrome in a pregnant mother suspected to have a mild expression of this autosomal dominant condition. However, in sporadic cases with lack of a family history for this rare syndrome, prenatal diagnosis may be difficult to ascertain.

Adult↗
PubMed2000

Fetal ovarian cysts: a report of three cases managed by intrauterine aspiration.

Small follicular or functional theca-lutein cysts are a common finding in fetal and neonatal ovaries. After delivery, decrease of hormonal stimulation may lead to spontaneous resolution of the cyst. A high rate of complication has been underlined by recent studies, the most common being ovarian torsion with subsequent loss of the ovary. Because torsion may happen with any size of cyst, however large or small, we suggest in utero decompression even in small fetal ovarian cysts (< 5 cm). We report here three cases of such cysts managed by intrauterine aspiration with good outcome and no further need for neonatal surgery. In all cases cytology of the cyst aspirate demonstrated numbers of granulosa cells and fluid biochemistry showed a high amount of estradiol, progesterone, and testosterone that confirmed the etiology as ovarian. Despite the small size of the cysts, no technical difficulties were encountered and no maternal or fetal morbidity occurred. Prenatal management of fetal ovarian cysts remains controversial, however, and our limited experience needs to be assessed on a larger number of cases.

Adult↗
PubMed2000

Effects of testosterone replacement in hypogonadal men.

Treatment of hypogonadal men with testosterone has been shown to ameliorate the effects of testosterone deficiency on bone, muscle, erythropoiesis, and the prostate. Most previous studies, however, have employed somewhat pharmacological doses of testosterone esters, which could result in exaggerated effects, and/or have been of relatively short duration or employed previously treated men, which could result in dampened effects. The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density, muscle mass and strength, erythropoiesis, prostate volume, energy, sexual function, and lipids in previously untreated hypogonadal men. We selected 18 men who were hypogonadal (mean serum testosterone +/- SD, 78 +/- 77 ng/dL; 2.7 +/- 2.7 nmol/L) due to organic disease and had never previously been treated for hypogonadism. We treated them with testosterone transdermally for 3 yr. Sixteen men completed 12 months of the protocol, and 14 men completed 36 months. The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment. Bone mineral density of the lumbar spine (L2-L4) increased by 7.7 +/- 7.6% (P < 0.001), and that of the femoral trochanter increased by 4.0 +/- 5.4% (P = 0.02); both reached maximum values by 24 months. Fat-free mass increased 3.1 kg (P = 0.004), and fat-free mass of the arms and legs individually increased, principally within the first 6 months. The decrease in fat mass was not statistically significant. Strength of knee flexion and extension did not change. Hematocrit increased dramatically, from mildly anemic (38.0 +/- 3.0%) to midnormal (43.1 +/- 4.0%; P = 0.002) within 3 months, and remained at that level for the duration of treatment. Prostate volume also increased dramatically, from subnormal (12.0 +/- 6.0 mL) before treatment to normal (22.4 +/- 8.4 mL; P = 0.004), principally during the first 6 months. Self-reported sense of energy (49 +/- 19% to 66 +/- 24%; P = 0.01) and sexual function (24 +/- 20% to 66 +/- 24%; P < 0.001) also increased, principally within the first 3 months. Lipids did not change. We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip, fat-free mass, prostate volume, erythropoiesis, energy, and sexual function. The full effect of testosterone on bone mineral density took 24 months, but the full effects on the other tissues took only 3-6 months. These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men.

Administration, Cutaneous↗
PubMed1999

A Drosophila CDK5alpha-like molecule and its possible role in response to O(2) deprivation.

Cyclin-dependent kinase 5 activator (Cdk5alpha) is an activator of Cdk5 kinase activity and its expression is restricted to neurons. The complex of Ckd5/Cdk5alpha is essential for neurite outgrowth during neuronal differentiation and possibly also for neuronal degeneration. Here we report the isolation and characterization of a Drosophila Cdk5alpha-like molecule (dCdk5alpha). The gene encoding this molecule is localized in the Drosophila chromosome region of 31D1-31D2. The expression of this gene is differentially regulated with a very low level at earlier developmental stages and reaches the highest level in the adult. The C-terminal of this molecule shares high homology with the mammalian Cdk5alpha molecule. Constitutive over-expression of dCdk5alpha in transgenic flies significantly prolongs their recovery time from 5 min to O(2) deprivation or anoxia in older flies (15 days) but not in young ones (4 days). In addition, anoxia up-regulated the expression of this gene. Taken together, the results in this report and others provide a framework for genetically dissecting the functions of Cdk5alpha/Cdk5 complex in the CNS.

Amino Acid Sequence↗
PubMed1999

Renal angiotensin II receptor regulation and renin-angiotensin system inhibition in one-kidney, one clip hypertensive rats.

OBJECTIVE: To characterize glomerular and preglomerular vascular angiotensin II receptors during the acute phase of nonrenin-dependent one-kidney, one clip hypertension in rats, using the angiotensin II antagonists losartan and PD 123319, and to investigate their regulation after renin-angiotensin system blockade with either an angiotensin converting enzyme inhibitor, captopril, or an angiotensin II receptor antagonist, TCV-116. MATERIALS AND METHODS: One-kidney, one clip hypertension was produced in male Sprague-Dawley rats by placing a silver clip (internal diameter 0.2 mm) on the left renal artery and removing the contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their glomerular and preglomerular vascular membranes were purified. Competitive binding studies were performed using specific angiotensin II antagonists. Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks before treatment with captopril or TCV-116 for 2 weeks. RESULTS: Competitive binding studies showed that only the angiotensin II type 1 (AT1) receptor was detected on both glomeruli and preglomerular vessels of all groups. The vascular AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one clip groups, but the glomerular receptor density was not different in these rats compared with age-matched uninephrectomized controls. The glomerular receptor density was significantly higher in captopril-treated rats and significantly lower in TCV-116-treated rats compared with untreated and control rats, but no significant changes were detected in any groups in vascular AT1 receptor density. CONCLUSIONS: Angiotensin II receptors on preglomerular vessels and glomeruli are differentially regulated during the early phase of hypertension and after renin-angiotensin system blockade. Vascular angiotensin II receptors are upregulated in the early phase of hypertension whereas glomerular angiotensin II receptors are not However, after renin-angiotensin system blockade, glomerular but not vascular angiotensin II receptors were differentially regulated according to the type of blockade.

Angiotensin Receptor Antagonists↗
PubMed1998

In vitro evaluation of the reliability of the Endex electronic apex locator.

A new generation of electronic apex locators (Endex) that operates in moistened canals has been developed lately. An experimental comparison of this apparatus with the real, tactile, and radiographic measurements of the root canal length has been conducted. Results show that tactile determination is highly inaccurate and that the Endex is as accurate as radiographic measurements. It also demonstrates that the nonreproducibility of radiographic measurements is statistically significant, whereas that of the Endex is not significant.

Dental Instruments↗
PubMed1998

Diagnosis of deep venous thrombosis by use of soluble necrosis factor receptor.

The purpose of this clinical study was to find a relationship between soluble tumor necrosis factor (TNF) receptor, deep venous thrombosis (DVT), and pulmonary emboli (PE). Clinical diagnosis of deep venous thrombosis and pulmonary emboli is a major dilemma for the clinician. Most existing tests are technician dependent, are expensive, or require sophisticated equipment. Advances in molecular biology will permit investigation of the value of TNF receptor as a test for screening, diagnosis, and evolution of DVT and PE. Forty patients with diagnosis of DVT, documented by real-time ultrasound imaging, were the subject of this clinical study. Five cc of plasma from each patient was studied by enzyme-linked immunosorbent assay (Elisa) for measurement of soluble TNF receptor. Significantly increased concentration of plasma-soluble TNF receptor was present in patients with DVT as opposed to normal individuals. There was a close relationship between plasma concentration of soluble TNF receptor and evaluation of the disease. In this preliminary clinical study, it appears that plasma measurement of soluble TNF receptor could be used as a clinical test for diagnosis of DVT and PE.

Adult↗
PubMed1998

Is it hyperthyroidism? You can't always tell from the clinical picture.

Hyperthyroidism usually causes a typical clinical syndrome in younger patients, but in some cases it presents with only minimal or atypical symptoms. This is especially true in older patients, who may have none of the typical signs, such as goiter. Differentiation between a euthyroid hyperthyroxinemic state and hyperthyroidism is crucial to avoid unnecessary treatment of persons with a normally functioning thyroid gland. In addition, distinguishing between causes of hyperthyroidism is important, because the treatments may be completely different. For example, in subacute thyroiditis, supportive care and observation are usually the only treatments needed, whereas in Graves' disease or toxic multinodular goiter, more definitive therapy is required.

Adult↗
PubMed1997

P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy.

BACKGROUND: Fewer than 20% of patients with bone cancer who are treated with surgery alone are cured. Even with the best current treatment, surgery combined with chemotherapy, only 60%-80% of patients with nonmetastatic bone cancer and 10% of patients with metastatic bone cancer are cured. Thus far, the reason for treatment failure in the nonresponding subset has not been identified. It has been hypothesized that P-glycoprotein, which confers multidrug resistance, might be the cause. We sought to determine whether the expression of P-glycoprotein is associated with poor treatment outcome in osteosarcoma. METHODS: In a retrospective study, we correlated P-glycoprotein expression with the outcome of conventional chemotherapy in 62 consecutive, clinically staged patients diagnosed as having osteosarcoma between 1980 and 1989. RESULTS: P-glycoprotein was overexpressed in 27 patients but not in another 34 patients, and expression was ambiguous in the sample from one patient. At a median follow-up of 8.9 years, the 34 patients whose tumors did not express P-glycoprotein had significantly better relapse-free rates than the 27 subjects whose tumors expressed the protein (87% versus 0%; P<.00001) and had improved survival rates (94% versus 35%; P<.00001). Among the 46 patients who received chemotherapy before surgery, the 23 whose tumors were negative for P-glycoprotein showed significantly better long-term outcomes (P<.00002), although differences in tumor necrosis in response to therapy were only of borderline significance (P = .057). CONCLUSIONS: P-glycoprotein expression does correlate with treatment failure in patients with osteosarcoma. This correlation raises the possibility that inhibiting the action of P-glycoprotein as part of therapy for this disease would improve outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Sensitive immunofluorescence detection of the expression of P-glycoprotein in malignant cells.

Because reversal of multidrug resistance increases chemotoxicity, early detection of low P-glycoprotein expression is clinically relevant for justifying early treatment of those patients that might benefit most from reversal therapy. We elected to score P-glycoprotein in single tumor cells, because the gene is rarely amplified, mRNA levels do not necessarily correlate with protein levels, and many normal hematopoietic or stroma cells within tumors and leukemic marrows also express P-glycoprotein. We enhanced the "signal-to-noise" ratio for detecting low P-glycoprotein levels by a novel complex made by pre-incubating mouse peroxidase-antiperoxidase, used solely to provide a stable framework for attaching multiple DTAF-labeled F(ab')2 fragments of rabbit antimouse IgG. We improved specificity by using both C219 and C494, which are directed against separate internal P-glycoprotein epitopes. We standardized staining with two series of negative and positive controls, in which P-glycoprotein was quantified by immunoblot, and confirmed sensitivity by staining a low-expression cell line and "mixed" samples containing small numbers of positive cells. We measured P-glycoprotein by flow cytometry, examining aliquots by differential interference contrast microscopy to identify malignant cells, in which we confirmed P-glycoprotein staining by fluorescence microscopy. We detected low P-glycoprotein expression in clinical samples of leukemic blasts, distinguishing them from normal P-glycoprotein-expressing hematopoietic cells. This assay may be valuable for early diagnosis of low, but potentially important expression of P-glycoprotein, thereby allowing early application of reversal therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein.

Failure of chemotherapy associated with expression of the multidrug resistance protein p170 frequently occurs in retinoblastoma (RB). Despite using cyclosporine, which inhibits p170 and improves our chemotherapy results, rare failures occur. In nonmetastatic primarily enucleated RBs, we show expression of p170 in 3 of 18 samples and expression of multidrug resistance protein (MRP), the second protein associated with resistance to chemotherapy, in 1 of 18 samples. All three RBs that failed chemotherapy without cyclosporine expressed MRP with p170. All three RBs that were enucleated immediately when chemotherapy failed despite the addition of cyclosporine expressed only MRP. One RB enucleated 2 years after failing chemotherapy with cyclosporine, despite radiation and salvage chemotherapy, expressed both p170 and MRP. Two metastatic RBs that expressed both p170 and MRP at diagnosis and at recurrence failed chemotherapy without cyclosporine, whereas one metastatic RB that expressed neither protein was cured by chemotherapy without cyclosporine. MRP may result in failure of chemotherapy despite the elimination of p170-expressing clones by cyclosporine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Modulation of renal glomerular angiotensin II receptors by ace inhibition and AT1 receptor antagonism.

Angiotensin-converting enzyme inhibitors (ACE-I) and specific nonpeptide angiotensin II (ANG II) receptor antagonists have been used extensively to treat a variety of cardiovascular disorders in experimental animals and humans. Despite their widespread use, only a limited amount of data has been published regarding the effect that renin-angiotensin system (RAS) blockade may have on ANG II receptors, and very often this information is contradictory. The present study was designed to investigate whether changes in plasma ANG II levels induced by RAS blockade could alter glomerular ANG II receptor characteristics. Captopril was employed as an ACE-I with losartan and TCV-116, two AT1 receptor antagonists of different chemical structure. Two experimental protocols were established. Protocol 1 contained 3 experimental groups: controls (Sprague-Dawley rats, 250-300 g BW), and animals treated with either captopril (0.5 g/l via drinking water) or losartan (10 mg/kg BW p.o.). In protocol 2, the animals were treated as in protocol 1 except that losartan was replaced by TCV-116 (1 mg/kg BW p.o.). At the end of treatment (3 days), all groups were killed by decapitation, blood was collected for plasma renin activity (PRA) measurement, and hearts and kidneys were excised. ANG II receptors were assessed by radioligand binding assays on membrane preparations of purified glomeruli, by displacement of 125I-[Sar1, Ile8]-ANG II with specific nonpeptide antagonists of AT1 (losartan) and AT2 (PD 123319) receptor subtypes. RAS blockade by either ACE-I or AT1 antagonists increased PRA. The binding assays showed that renal glomeruli from treated rats and controls expressed a single population (AT1) of ANG II receptors. The density of glomerular AT1 receptors was not modulated by captopril, but was significantly lower in animals treated with either losartan (Bmax: 854 +/- 169 vs. 379 +/- 79 fmol/mg protein and Kd: 59 +/- 6 vs. 45 +/- 6 nM for controls and losartan, respectively) or TCV-116 (480 +/- 72 vs. 188 +/- 16 fmol/mg protein and Kd: 45 +/- 9 vs. 37 +/- 18 nM for controls and TCV-116, respectively) than in their controls. No changes in receptor affinity (Kd) were detected. Previous membrane "acid-wash" did not modify the results. We conclude that short-term RAS blockade by AT1 antagonists, but not by ACE-I, induces true downregulation of renal glomerular ANG II receptors. No AT2 receptor subtype was detected.

Angiotensin II↗
PubMed1997

Effect of angiotensin-converting enzyme two-week inhibition on renal angiotensin II receptors and renal vascular reactivity in SHR.

We recently reported that intrarenal vascular AT1 angiotensin II (ANG II) receptors are major determinants of the increased vascular resistance and reactivity to ANG II observed in the kidney of spontaneously hypertensive rats (SHR). We decided to test the hypothesis that, by modifying plasma ANG II levels by inhibiting the ANG II-converting enzyme (ACE) with captopril, we would modify intrarenal ANG II receptors, and therefore the renal vascular response to ANG II. Two approaches were taken: (1) radioligand binding assays were performed on membrane preparations of purified renal microvessels and glomeruli, with displacement of 125I-[Sar-Ile8]-ANG II by specific non-peptide antagonists of AT (losartan) and AT2 (PD 123319): (2) dose-response curves to ANG II on the isolated perfused kidney were studied. Two weeks of captopril treatment significantly reduced blood pressure (BP) and relative heart weight, and increased plasma renin activity. The binding assays showed that renal microvessels and glomeruli expressed a single receptor population (AT1) for ANG II. The density of glomerular AT1 was not modulated by captopril treatment (600 +/- 174 v 573 +/- 97 fmol/mg protein in non-treated and treated SHR respectively); however. AT1 density on the intrarenal arteries increased 3-fold (55 +/- 20 v 154 +/- 30 fmol/mg protein in non-treated and treated SHR respectively. P < 0.05). Experiments with isolated perfused kidneys demonstrated that captopril did not improve the compliance of intrarenal vessels to high flow but increased their reactivity to ANG II (ED50 = 18 nM v 0.5 pM, P < 0.01). We conclude that treatment with an ACE inhibitor increases vascular reactivity to ANG II which may be mediated by an upregulation of renal vascular ANG II receptors.

Angiotensin II↗