Synthetic UDP-furanoses as potent inhibitors of mycobacterial galactan biogenesis.

UDP-galactofuranose (UDP-Galf) is a substrate for two types of enzymes, UDP-galactopyranose mutase and galactofuranosyltransferases, which are present in many pathogenic organisms but absent from mammals. In particular, these enzymes are involved in the biosynthesis of cell wall galactan, a polymer essential for the survival of the causative agent of tuberculosis, Mycobacterium tuberculosis. We describe here the synthesis of derivatives of UDP-Galf modified at C-5 and C-6 using a chemoenzymatic route.

Probing UDP-galactopyranose mutase binding pocket: a dramatic effect on substitution of the 6-position of UDP-galactofuranose.

UDP-galactopyranose mutase (UGM) catalyzes the isomerization of UDP-galactopyranose (UDP-Galp) into UDP-galactofuranose (UDP-Galf), an essential step of the mycobacterial cell wall biosynthesis. UDP-(6-deoxy-6-fluoro)-D-galactofuranose 1 was tested as substrate of UGM. Turnover could be observed by HPLC.

Engineering ribonucleoside triphosphate specificity in a thymidylyltransferase.

Nature's glycosylation catalysts, glycosyltransferases, indirectly manipulate and control many important biological processes by transferring sugar nucleotide donors onto acceptors. Challenging chemical synthesis impedes synthetic access to sugar nucleotides and limits the study of many glycosyltransferases. Enzymatic access to sugar nucleotides is a rapidly expanding avenue of research, limited only by the substrate specificity of the enzyme.

Recent knowledge and innovations related to hexofuranosides: structure, synthesis and applications.

Hexofuranosides are widely spread in nature, and notably in numerous pathogenic microorganisms. This particular five-membered ring for hexosides leads to novel biological properties and, as usual in glycochemistry, to completely different reactivity and selectivity. Far from being exhaustive, this review will first focus on the structure of the oligosaccharidic part of hexofuranosyl conjugates found in natural sources.

4-Nitro-phenyl α-l-rhamnopyran-oside hemihydrate.

In the title compound, C(12)H(15)NO(7)·0.5H(2)O, there are two independent mol-ecules in the asymmetric unit, together with one water molecule. The pyran-oside rings each have close to a (1)C(4) chair conformation and the nitro groups are almost coplanar with the benzene rings.

Enzyme-catalyzed synthesis of furanosyl nucleotides.

A bacterial alpha-d-glucopyranosyl-1-phosphate thymidylyltransferase was found to couple four hexofuranosyl-1-phosphates, as well as a pentofuranosyl-1-phosphate, with deoxythymidine 5'-triphosphate, providing access to furanosyl nucleotides. The enzymatic reaction mixtures were analyzed by electrospray ionization mass spectrometry and NMR spectroscopy to determine the anomeric stereochemistry of furanosyl nucleotide products. This is the first demonstration of a nucleotidylyltransferase discriminating between diastereomeric mixtures of sugar-1-phosphates to produce stereopure, biologically relevant furanosyl nucleotides.

Versatile synthesis of rare nucleotide furanoses.

Direct activation of unprotected thioimidoyl furanosides yielded in only one step and few minutes a panel of rare uridine 5'-diphospho-furanoses. Diastereoselectivity of the reaction was tightly connected with reaction time, temperature, and nature of the furanosyl donor. This approach was totally selective since no ring expansion from the initial five-membered ring to the more stable pyranose form was observed.

Radioimmunodetection of medullary thyroid carcinoma using indium-111 bivalent hapten and anti-CEA x anti-DTPA-indium bispecific antibody.

Unlabelled: Pretargeting labeled bivalent hapten with bispecific antibodies has proven feasible in the clinic, and our earlier results have suggested the technique may be very sensitive for detecting small recurrences and metastases. Medullary thyroid carcinoma (MTC) is an example where this technique may be the most useful since local recurrences and isolated metastases are removed surgically when detected, and thyrocalcitonin provides a specific and sensitive tumor marker. In our current study, we evaluated pretargeted immunoscintigraphy in a larger number of MTC patients.

Two-step immunoscintigraphy for non-small-cell lung cancer staging using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer.

Unlabelled: Immunoscintigraphy (IS) using anti-CEA F(ab')2 monoclonal antibody (MAb) is useful for improving mediastinal staging of nonsmall cell lung cancer (NSCLC), but the technique was limited because of an insufficient contrast between tumor and normal tissues. The aim of this study was to determine if the method could be improved by a two-step method which uses a bispecific anti-CEA/anti-di-DTPA antibody (Bs-MAb) and 111In-labeled di-DTPA-tyrosyl-lysine bivalent hapten.

Methods: Twelve patients were intravenously given a 30 min Bs-MAb infusion (0.

Bispecific antibody and iodine-131-labeled bivalent hapten dosimetry in patients with medullary thyroid or small-cell lung cancer.

Unlabelled: The purpose of this study was to estimate the dose delivered to tumor targets and normal tissues after two-step injection of an anti-CEA/anti-DTPA-In (F6-734) bispecific antibody and a 131I-labeled di-DTPA in-TL bivalent hapten in patients with medullary thyroid carcinoma (MTC) and small-cell lung cancer (SCLC).

Methods: Five patients with persistent disease or recurrences of MTC and five patients with primary SCLC or relapse were studied. In a first step, 0.

131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas.

Objective: Most incidentally discovered adrenal tumours ('incidentaloma') are benign adrenocortical adenomas. It has been suggested that 131I-6 beta-iodomethylnorcholesterol (IMC) scan could specify the degree of functional autonomy of such adenomas depending on whether they prevent contralateral adrenal tracer uptake. Our purpose was to examine this hypothesis in a correlated scintigraphic and endocrine study.

Induction of anaesthesia by propofol and hepatic blood flow in the rabbit.

Effects of propofol (12.5 mg kg-1, i.v.

Angiomagnetic resonance imaging of iliofemorocaval venous thrombosis.

Although magnetic resonance imaging has been proposed for the diagnosis of deep venous thrombosis (DVT), its role in diagnostic strategy remains to be defined. We compared prospectively magnetic resonance angiography (MRA) with two-dimensional time-of-flight with contrast venography (CV) and colour duplex sonography (CDS) in 25 patients with DVT of the pelvis confirmed by CV. All patients were examined by CV (gold standard) and MRA and 17 by CDS.

Bifunctional antibodies for radioimmunotherapy.

In two-step targeting technique using bifunctional antibodies, a nonradiolabeled immunoconjugate with slow uptake kinetics (several days) is initially injected, followed by a small radiolabeled hapten with fast kinetics (several hours) that binds to the bispecific immunoconjugate already taken up by the tumor target. In patients with colorectal or medullary thyroid cancer, clinical studies performed with an anti-CEA/anti-DTPA-indium bifunctional antibody and an indium-111-labeled di-DTPA-TL bivalent hapten showed that tumor uptake was not modified compared to results for F(ab')2 fragments of the same anti-CEA antibody directly labeled with indium-111, whereas the radioactivity of normal tissues was significantly reduced (3- to 6-fold). The fast tumor uptake kinetics (several hours) and high or very high tumor-to-normal tissue ratios obtained with the bifunctional antibody technique are favorable parameters for efficient radioimmunotherapy.

Pretargetted imaging of colorectal cancer recurrences using an 111In-labelled bivalent hapten and a bispecific antibody conjugate.

In 11 patients recurrence of colorectal cancer was suspected by a rise in serum carcinoembryonic antigen (CEA) (nine cases), by a subocclusive clinical situation (one case) or by endoscopy (on an anastomosis, one case). Two-step tumour targetting was performed by a first injection of 0.1 mg kg-1 of unlabelled bispecific antibody conjugate (an anti-CEA Fab' fragment chemically coupled to an anti-diethylene triamine pentaacetate (DTPA)-indium fragment) followed 4 to 5 days later by injection of the bivalent DTPA hapten labelled with 5 to 8 mCi 111In.

[Diagnosis of venous thrombosis. Evaluation of immunoscintigraphy with 99M technetium labelled antifibrin].

Objectives: We evaluated the interpretation, reliability and usefulness of 99m technetium labelled antifibrin immunoscintigraphy for the diagnosis of deep vein thrombosis in the lower limbs.

Methods: The diagnostic value of 99m technetium labelled antifibrin immunoscintigraphy was assessed in 44 patients with suspected venous thrombosis. The reference examination was bilateral ascending phlebography; 40 patients had doppler ultrasonography of the veins; 0.

99Tcm-labelled anti-fibrin Fab' fragment for evaluating the course of venous thrombosis in the rabbit.

Immunoscintigraphy was performed using the Fab' fragment of 99Tcm-labelled T2G1s anti-fibrin monoclonal antibody in a rabbit experimental model of venous thrombosis of known and increasing age (1, 3 and 7 days). Scans were positive in 3/7 cases for 1-day thrombosis (fibrin-poor network) and in 7/7 cases for 3-day thrombosis (fibrin-rich network). In rabbits with 7-day thrombosis, the scan was positive (2/4 cases) only when connective tissue was not present in the clot.

[Pelvic phlebitis presenting as paradoxical arterial embolism].

The authors report the case of a 24-year-old woman with paradoxical embolism of the right arm subsequent to childbirth. Patent foramen ovale was diagnosed by right cardiac catheterization and contrast echocardiography. On the basis of clinical, immunoscintigraphic and radiologic data, the pelvic region was the only possible origin of the embolic process.

Detection of lung and bone infection with anti-granulocyte monoclonal antibody BW 250/183 radiolabelled with 99Tcm.

Twenty-four patients with suspected infection (eight bone, 16 lung) were studied using monoclonal antibody BW250/183 which recognizes epitopes present on the surface of granulocytes. Bronchofibroscopic samples (microbiological studies and alveolar cell counts) were obtained from 14/16 patients with lung disease. Bronchofibroscopy isolated a micro-organism nine times.

Radioimmunodetection of medullary thyroid cancer using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer.

Two-step radioimmunotargeting using a bispecific anti-CEA/anti-in-DTPA monoclonal antibody and an 111In-labeled DTPA dimer (diDTPA-TL) was evaluated nine times in eight patients with medullary thyroid cancer (MTC). Immunoscintigraphy was performed 5 and 24 hr after injection of 111In-diDTPA-TL. For five patients, radioimmunoguided surgery (RIGS) was performed using a hand-held gamma probe (sodium iodine), and a biodistribution study was performed 48 hr (four times) and 24 hr (one time) after injection of 111In-diDTPA-TL.

Lung distribution and pharmacokinetics of aerosolized tobramycin.

Aminoglycosides are commonly used in the treatment of nosocomial pneumonia in association with beta-lactams. Unfortunately, penetration of intravenously administered aminoglycosides into the lung tissue remains low. In animal models, aerosolization of these drugs provides high lung concentrations and low serum levels.

Usefulness of imaging ovarian cancer recurrence with In-111-labeled monoclonal antibody (OC 125) specific for CA 125 antigen. The INSERM Research Network (Nantes, Rennes, Reims, Vuillejuif, Saclay.

Background: A progressive rise in serum CA 125 concentration during follow-up monitoring of ovarian cancer after treatment of primary tumor is suggestive of a recurrence.

Patients And Methods: A study was carried out in 19 patients with suspected recurrence of a previously treated ovarian carcinoma. All patients underwent ultrasonography (US), computed tomography (CT) and immunoscintigraphy (IS) using F(ab')2 fragments of indium-111-labeled OC 125 monoclonal antibody (specific for CA 125 antigen).

[The role of adrenal gland x-ray computed tomography and scintigraphy using radiolabelled norcholesterol in the etiological diagnosis of primary hyperaldosteronism].

The major etiologies of primary aldosteronism are aldosterone-producing adrenal adenoma, requiring a surgical treatment, and bilateral hyperplasia, usually managed with medical therapy. We only report a retrospective study on 22 patients with primary aldosteronism diagnosed by clinical and usual biochemical tests. All the patients were explored by computed tomography scan (CT) and iodomethyl-norcholesterol scintigraphy.

Experimental venous thrombosis: what animal model?

A new experimental venous thrombosis model is described and its role relative to other models is defined. Previous models are not satisfactory for all types of investigation. Opposite, present model based on the three classic thrombogenic factors is suitable for venous scintigraphy and evaluation of different forms of therapy for venous thrombosis of the limbs.