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Biomedical subjects

J Lambert

Publications and source records attributed to J Lambert.

At least 55 records · Page 3Linked to original sources
PubMed2000

Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection.

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.

Adult↗
PubMed2000

Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes.

Melanocytic dendrites consist of a central core of microtubules (MT) and a subcortical actin network. In previous reports we showed the presence of MT-associated motor proteins kinesin and cytoplasmic dynein on the melanosomal surface, forming a link with MT (Vancoillie et al. J Invest Dermatol 2000;114:421-429; Vancoillie et al. Br J Dermatol 2000;143:258-306). We could also demonstrate the association of kinectin, the kinesin receptor, with melanosomes. The interaction of cytoplasmic dynein with its cargoes is thought to be indirectly mediated by dynactin, a complex that binds to the dynein intermediate chain. Therefore, in this study, we investigated the in vitro expression of dynactin subunits P150Glued and P50 in normal human epidermal melanocytes, keratinocytes, and dermal fibroblasts by reverse transcription-polymerase chain reaction and northern blot analysis. In an attempt to gain an insight into the subcellular localization of dynactin, immunofluorescence and immunoelectron microscopy (IEM) studies were performed. The two isoforms of P150Glued and P50 are expressed in all studied skin cells. Immunofluorescence staining shows punctate distributions for P150Glued and P50 in melanocytes. P150Glued shows a clear centrosomal staining and accentuation in the dendrite tips. P50 is also accentuated in the perinuclear area and dendrite tips. Immunofluorescence double-labeling with a melanosome marker showed apparent colocalization of both P150Glued and P50 with melanosomes. By IEM, P50 is detected on the surface of the majority of melanosomes in melanocytes. The colocalization of different subunits of the dynactin complex with melanosomes is consistent with the earlier finding of cytoplasmic dynein association with melanosomes and supports the hypothesis that this complex could form a link between cytoplasmic dynein and the melanosomal membrane.

Blotting, Northern↗
PubMed2000

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study.

BACKGROUND: The efficacy of omeprazole-based eradication therapies has been determined mostly in populations with low to moderate prevalence of metronidazole resistant Helicobacter pylori, yet resistance is high in many regions. AIM AND METHODS: The H. pylori eradication and duodenal ulcer healing rates after 1 week of either omeprazole 40 mg mane, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM) or omeprazole 20 mg b.d., metronidazole 400 mg b. d. and clarithromycin 250 mg b.d. (OMC) were compared in a randomized trial in Australia and New Zealand. Patients had a further 1 week of omeprazole 20 mg. Outcome was assessed at 6 weeks with stringent criteria (endoscopy, biopsies and 13C-urea breath test). RESULTS: Of 220 subjects randomized, the H. pylori eradication rates (all patients treated/per protocol) were 82%/85% for OMC and 58%/63% for OAM (P= 0.001). Pre-treatment metronidazole resistance was present in 56% and clarithromycin resistance in 6%. The eradication rate for primary metronidazole resistance isolates treated with OMC was 80% (CI: 65-90%) compared with 45% (CI: 29-62%) for OAM, whereas for sensitive organisms, the eradication rates were 94% (CI: 79-99%) and 79% (CI: 62-91%), respectively. Duodenal ulcer healing was 96% for OMC and 87% for OAM. Compliance was excellent and both treatments were well-tolerated. CONCLUSIONS: OMC is a well-tolerated, effective therapy for H. pylori eradication and duodenal ulcer healing in this region despite the high metronidazole resistance rate. OAM is less effective, largely due to the impact of metronidazole resistance.

Adolescent↗
PubMed2000

Cytoplasmic dynein colocalizes with melanosomes in normal human melanocytes.

BACKGROUND: Melanocytic dendrites consist of a central core of microtubules and a subcortical actin network. Several studies provide arguments supporting the hypothesis that actin-based and microtubule-based motor proteins co-operate in melanosome transport towards the dendrite tips. Melanosomes can move bidirectionally along microtubules in vitro, and in murine melanocytes, they move towards the cell periphery and back again. Microtubules have a fast-growing plus end and a slow-growing minus end. Microtubule-associated motor proteins move unidirectionally either towards the plus or towards the minus end. However, it is not known which motor protein is responsible for minus end-directed movement of melanosomes. OBJECTIVES: We aimed to investigate the in vitro expression of the minus end-directed motor protein cytoplasmic dynein in normal human epidermal melanocytes, keratinocytes and dermal fibroblasts. METHODS: Reverse transcription-polymerase chain reaction and Northern blot analysis were used. In addition, an attempt to obtain insight into the subcellular localization of cytoplasmic dynein, immunofluorescence studies and immunogold electron microscopic studies were performed. RESULTS: The three different forms of cytoplasmic dynein heavy chain were expressed in all studied skin cells. Immunofluorescence staining showed similar punctate distributions for dynein heavy chain 1 and dynein heavy chain 2 in melanocytes, with accentuation in the perinuclear area and dendrite tips. Double labelling with a melanosome marker showed apparent co-localization of both dynein heavy chains 1 and 2 with melanosomes in the perinuclear area and dendrite tips. For the dynein intermediate chain of 74 kDa, again a punctate staining pattern was seen with intense centrosomal staining. A close association of dynein intermediate chain 74 and alpha-tubulin with the melanosome surface was detected using immunogold electron microscopy. CONCLUSIONS: The colocalization of different subunits of the cytoplasmic dynein complex with melanosomes is consistent with the hypothesis that this motor protein supports minus end-directed melanosome movement along microtubules.

Adult↗
PubMed2000

ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type 1 diabetic patients.

BACKGROUND: The usefulness of treatment with an angiotensin-converting enzyme-inhibitor (ACE-inhibitor) in normotensive patients with type 1 diabetes is controversial. We investigated whether ACE-inhibition improves endothelial function in such patients and compared the responses to those in healthy subjects. DESIGN: We studied 23 healthy volunteers (controls, aged 29.8 [SD 7.0] years) and 24 type 1 diabetic patients (aged 28.7 [9. 6] years; HbA1c 8.1 [1.2]%; diabetes duration 13.8 [2-30] years; blood pressure < 140/90 mm Hg; 7 with microalbuminuria) after 5 weeks of ACE-inhibition (quinapril, 10 mg day-1) and placebo in a randomized, double-blind cross-over design. Estimates of endothelial function obtained were by flow-mediated vasodilation and plasma levels of endothelium-derived proteins. RESULTS: As estimated from the measurements on placebo, type 1 diabetic patients, as compared to the controls, had some impairment of endothelial function: plasma tissue-type plasminogen activator levels were lower (3.5 vs. 5.4 ng mL(-1), P<0.05), but there were no significant differences in brachial artery flow-mediated vasodilation or plasma levels of von Willebrand Factor, endothelin-1, plasminogen activator inhibitor-1, soluble E-selectin or vascular cell adhesion molecule-1. As compared to placebo, ACE-inhibition increased flow-mediated vasodilation in controls (by 3.84% points [95% CI, 0.66 - 7.02], P<0.05), but not in type 1 diabetic patients (0.82% points [95% CI, -2.72 - 4.36], P = 0.64; P = 0.08 vs. controls). On ACE-inhibition soluble E-selectin levels decreased both in controls (from 43.0 to 37.0 ng mL(-1), P<0.01) and in type 1 diabetic patients (from 41.0 to 39.0 ng mL(-1), P = 0.09). Other endothelial markers did not change during ACE-inhibition. CONCLUSION: Normotensive type 1 diabetic patients with normoalbuminara or microalbuminuria have mild endothelial dysfunction. Short-term ACE-inhibition improves endothelial function as reflected by a decreased sE-selectin in healthy subjects and in normotensive type 1 diabetic patients. In healthy subjects, ACE-inhibition increases flow-mediated vasodilation. In contrast, in type 1 diabetic patients, ACE-inhibition does not affect flow-mediated vasodilation.

Adult↗
PubMed2000

In this issue

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

arg-cys substitution at codon 1246 of the human myosin Va gene is not associated with Griscelli syndrome.

Myosin Va is an actin-associated motor protein involved in organelle transport such as melanosomes and neuron synaptic vesicles and has always been proposed as the candidate gene for the autosomal recessive Griscelli-Pruniéras syndrome, one of the silvery hair syndromes, which is a lethal disease combining immunodeficiency and neurologic and pigmentary abnormalities. Thus far, two mutations in the myosin Va gene have been described to be associated with this syndrome. One of these mutations was a homozygous mis-sense mutation causing an arginine to cysteine alteration at codon 1246. Because we also found this particular substitution after mutation analysis of a Griscelli patient, we checked its relevance in a control group of 124 unrelated healthy individuals and found it to be present, even in homozygous state, in normal unaffected individuals. It is clear that this arg1246cys substitution is a polymorphism occurring in the human population and not occurring in association with Griscelli syndrome. Distinguishing a polymorphism from a bona fide mutation is of utmost importance and has major ethical implications with regard to prenatal genetic counseling in affected families.

Albinism↗
PubMed2000

Absence of telomerase activity and telemorase catalytic subunit mRNA in melanocyte cultures.

The classic model of activation of telomerase, for which activity has been found in most cancers including cutaneous malignant melanoma (CMM), dictates that enzyme activity is generated by pathological reactivation of telomerase in telomerase-negative somatic cells. However, recent data demonstrated physiological up-regulation in some normal cell types when established as proliferating cultures, indicating that, in some cancer types, telomerase is expressed by the process of up-regulation in telomerase-competent precursor cells. In this study, cultures of epidermal melanocytes, progenitor cells of CMM, were established and harvested in the logarithmic phase of growth. Telomerase activity was looked for using a non-isotopic variant of the telomeric repeat amplification protocol, and transcript expression of the hTERT gene, the rate-limiting catalytic telomerase subunit, was investigated by the reverse transcription polymerase chain reaction. Neither telomerase activity nor hTERT mRNA could be detected in proliferating melanocyte cultures. Our in vitro data argue against the model of telomerase as a common biomarker of cell proliferation. The results further suggest that telomerase is tightly controlled in normal melanocytes, and that telomerase is reactivated rather than up-regulated in melanocytic precursors during melanoma initiation or progression.

Catalytic Domain↗
PubMed2000

The implications and management of drug interactions with itraconazole, fluconazole and terbinafine.

The efficacy and safety of many pharmacological agents can be adversely affected by drug interactions. However, an appreciation of the mechanisms and incidence of these interactions, together with a knowledge of the patient's medical history, means that the majority are predictable and can be managed successfully. Drug interactions involving oral antifungal agents such as itraconazole, fluconazole and terbinafine have been studied extensively and are well understood. When problems are known to arise, they can often be overcome or minimised by varying the dosage regimens, or by drug monitoring. Where certain drugs are definitely contraindicated with antifungal agents, suitable alternatives can usually be found. Clinical trials and surveillance monitoring have demonstrated that when viewed in a wider context, drug interactions do not represent a particular safety problem for the newer oral antifungal agents. An improved understanding of the drug interaction processes and appropriate control measures mean that the high benefit-to-risk ratio of these medications can be maintained.

Administration, Oral↗
PubMed2000

Economic impact of febrile morbidity and use of permethrin-impregnated bed-nets in a malarious area I. Study of demographics, morbidity, and household expenditures associated with febrile morbidity in the Republic of Benin.

In preparation for a study on the effect of bed net use on malaria, this article describes febrile morbidity and malaria expenditures in a sub-Saharan area (Benin) of hyperendemic malaria. The 325 randomly selected households were visited weekly between April 1994 and March 1995 to determine febrile morbidity and household expenditures for prevention and treatment. The results indicate that rural children had two febrile episodes annually compared with 0.3 episodes among children living in the city. There was no difference in mean annual febrile episodes between adults and children (adults = 1.5, children = 1.5; P = 0.48) and in the expenditures per febrile episode (adults = US$1.85, children = US$1.62; P = 0.45). Annual prevention expenditures were higher for adults than for children (US$1.73 and US$1.28, respectively; P < 0.001), although there was no significant difference in expenditures for annual treatment for adults and children (US$2.15 and US$2.34, respectively). These and other findings are analyzed further and discussed.

Adult↗
PubMed2000

Economic impact of febrile morbidity and use of permethrin-impregnated bed nets in a malarious area II. Determinants of febrile episodes and the cost of their treatment and malaria prevention.

The objective of this study is to determine the effect of permethrin insecticide-treated bed net (PITN) use on the incidence of febrile episodes and on household malaria expenses in Benin. Over the course of one year, 208 randomly selected PITN user and non-user households were visited weekly to determine expenditures on febrile morbidity and its treatment, and to monitor spending on malaria prevention. Multivariate analyses were performed to distinguish the effects of PITN use from other important determinants of morbidity, such as malaria-related beliefs and practices, income, and other socio-economic variables. Results from the logistic regression analysis show that the use of PITNs decreases the risk of febrile episodes by 34% in children living in the rural zone. Multiple regression analysis reveals that PITN use does not reduce prevention and treatment expenses. These expenses are significantly associated with women's income. This report also discusses other factors associated with febrile morbidity and malaria-related expenditures.

Adult↗
PubMed2000

Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy.

BACKGROUND: The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment. PATIENTS AND METHODS: Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system. RESULTS: At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02). CONCLUSION: Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.

Age Factors↗
PubMed2000

[Generation of isolated words in normal subjects].

This study aims at analyzing the performance according to age, sex, and educational level in 112 French normal subjects on word generation tests, i.e., time-limited production of a noun or a verb semantically linked to a target "noun" or "verb". The nature of hits (exclusively production of nouns) has moreover been analyzed according to different features of the targets: noun vs verb, names of natural objects vs handmade objects, transitive vs intransitive verbs. Results show 1) a significant effect of age and educational level on performance, 2) a degree of difficulty, the verb/verb production test being significantly more difficult than the three other tests, 3) a convergency effect according to the natural vs handmade dichotomy, as subjects tend to produce, without specific instruction, an item belonging to the same category as that of the stimulus, and 4) object nouns tend to be produced in response to transitive verbs whereas subject nouns are not predominantly produced in response to intransitive verbs.

Adult↗
PubMed2000

[Epidemiology, physiopathology and treatment of a frequent ailment: tinea pedis].

Tinea pedis is an infection of the stratum corneum caused by dermatophytes. Nowadays, fitness centers, saunas, subtropical swimming pools and sport-shoes are more and more fashionable and are certainly responsible for the increase of cases of tinea pedis as dermatophytes grow preferentially in warm and humid environments. The clinical aspect is affected by several factors such as the host reaction to the infection, the virulence of the infective strain, species, and some local and environmental factors. If a dermatophytosis is suspected, it is mandatory to validate the provisional diagnosis by demonstration of the fungus (by culture or/and microscopic examination) to avoid useless and expensive treatments. The new antifungal molecules are very effective, well tolerated and allow short course of therapy improving the compliance of the patient in clinical practice. Relapse of tinea pedis is very common but could be avoided by several simple preventive measures of hygiene.

Antifungal Agents↗