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Biomedical subjects

M Weitz

Publications and source records attributed to M Weitz.

At least 19 recordsLinked to original sources
PubMed2003

Subclinical activation of latent cytomegalovirus (CMV) infection and anti-CMV immune response in patients with atopic dermatitis.

BACKGROUND: Microbiological infections are considered to be of pathophysiological importance in atopic dermatitis (AD). As yet, no information is available regarding cytomegalovirus (CMV) infection in this disease. This, however, is of interest because of the high prevalence of latent infections in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. OBJECTIVES: To investigate the prevalence of latent CMV infection, the frequency of active CMV infection, and the immune response to CMV in patients with moderate to severe AD. Methods To detect active infection we analysed CMV antigen expression by peripheral blood mononuclear cells (PBMC) from 27 patients with moderate to severe AD in comparison with 53 healthy volunteers. We used three monoclonal antibodies recognizing different CMV-encoded antigens and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique). RESULTS: Patients with AD had a higher mean frequency of CMV-positive PBMC: 2.25 per 10 000 vs. 0.74 per 10 000 in controls (P = 0.001) as well as a higher incidence of CMV antigenaemia: 29.6% vs. 7.5% (P < 0.01). Seropositivity for anti-CMV IgG antibodies indicated subclinical activation of latent infection. Remarkably, a clearance of CMV antigenaemia was observed during anti-eczematous treatment. Significantly higher plasma levels of tumour necrosis factor-alpha, which is involved in CMV reactivation, and interleukin-12, which is crucial for an antiviral cellular immune response, were observed in AD patients in comparison with healthy volunteers. Furthermore, a significantly enhanced frequency of circulating activated HLA-DR+ T cells especially in CMV-seropositive AD patients (19.3% vs. 13.5% in seronegative AD patients vs. 10.2% in controls) suggested that the active CMV infection triggers a cellular immune response. This was also supported by a high frequency of CMV-specific interferon-gamma-producing T cells in CMV-seropositive patients with AD. CONCLUSIONS: Our data suggest that active, subclinical CMV infection is more frequent in patients with moderate to severe AD and may have immunopathophysiological relevance.

Adult↗
PubMed2001

Superresolution of pulsed multiphoton Raman transitions.

We have investigated higher order multiphoton Raman resonances with two pulsed optical frequencies. Multiphoton transfer with up to 50 photons is observed with milliwatts of laser power. We demonstrate that the spectral width of the multiphoton resonances can be far below the Fourier transform linewidth of the driving optical pulses. The functional dependence of the transition linewidth on the number of exchanged photons is found to vary with the pulse shape. Our experiment is performed with laser-cooled rubidium atoms confined in a CO2-laser optical dipole trap.

Journal Article↗
PubMed2001

Controlled decoherence in multiple beam Ramsey interference.

We have scattered photons from an interfering path of a multiple beam Ramsey interference experiment realized with a cesium atomic beam. It is demonstrated that in multiple beam interference the decoherence from photon scattering cannot only lead to a decrease but, under certain conditions, also to an increase of the Michelson fringe contrast. In all cases, the atomic quantum state loses information with photon scattering, as "which-path" information is carried away by the photon field. We outline an approach to quantify this which-path information from observed fringe signals, which allows for an appropriate measure of decoherence in multiple path interference.

Journal Article↗
PubMed2000

Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive and increasingly used procedure in cases involving biliary and pancreatic diseases. However, the accuracy of MRCP in differential diagnosis between pancreatic cancer and chronic pancreatitis has never been documented in a large prospective controlled study. METHODS: 124 patients were recruited for the study, selected from 141 consecutive patients with an average age of 55 years (range 19-80) who presented to our department between February, 1996, and January, 1998, with a strong clinical suspicion of pancreatic cancer. MRCP images were interpreted by a radiologist and a gastroenterologist who were unaware of the clinical diagnosis of patients. The exact diagnosis was based upon histological evidence from biopsy examination (surgical and fine needle biopsy) or a follow-up of at least 12 months. FINDINGS: Of the 124 patients, 37 (30%) had pancreatic carcinoma; 17 (14%) had other neoplastic pancreatic diseases; 57 (46%) had chronic pancreatitis; 13 (10%) pancreatic ducts were clear. The sensitivity of MRCP with respect to diagnosing pancreatic cancer was 84% and its specificity 97%. The corresponding values for endoscopic retrograde cholangiopancreatography (ERCP) were 70% and 94%, respectively. INTERPRETATION: MRCP is as sensitive as ERCP when detecting pancreatic carcinomas. Furthermore, it is feasible to presume that the use of MRCP may prevent inappropriate explorations of the pancreatic and common bileducts in cases of suspected pancreatic carcinomas, where interventional endoscopic therapy (ie, palliative common-bileduct drainage) is unlikely.

Adult↗
PubMed2000

Measurement of the hydrogen 1S- 2S transition frequency by phase coherent comparison with a microwave cesium fountain clock

We report on an absolute frequency measurement of the hydrogen 1S-2S two-photon transition in a cold atomic beam with an accuracy of 1.8 parts in 10(14). Our experimental result of 2 466 061 413 187 103(46) Hz has been obtained by phase coherent comparison of the hydrogen transition frequency with an atomic cesium fountain clock. Both frequencies are linked with a comb of laser frequencies emitted by a mode locked laser.

Journal Article↗
PubMed2000

Phase coherent vacuum-ultraviolet to radio frequency comparison with a mode-locked laser

We demonstrate a versatile new technique that provides a phase coherent link between optical frequencies and the radio frequency domain. The regularly spaced comb of modes of a mode-locked femtosecond laser is used as a precise ruler to measure a large frequency gap between two different multiples (harmonics or subharmonics) of a laser frequency. In this way, we have determined a new value of the hydrogen 1S-2S two-photon resonance, f(1S-2S) = 2 466 061 413 187.29(37) kHz, representing now the most accurate measurement of an optical frequency.

Journal Article↗
PubMed2000

Choledochocele imaged with magnetic resonance cholangiography.

Choledochal cysts are rare developmental malformations of the biliary tree. Percutaneous and endoscopic ultrasound, as well as endoscopic retrograde cholangiopancreatography, are recommended diagnostic tools. Magnetic resonance cholangiography may also contribute to the workup and treatment plan of patients with choledochal cysts. We report a 25-yr-old white woman with episodic nausea and moderate epigastric discomfort. Magnetic resonance cholangiography showed a rather spherical, cyst-like, fluid-filled structure in continuity with the prepapillary segment of the common bile duct, thus making a choledochocele (type III choledochal cyst) likely. The patient was treated by endoscopic sphincterotomy and, after a 6-month follow-up, is without complaints.

Adult↗
PubMed2000

Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region.

Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.

Adenoma↗
PubMed1998

A prospective evaluation of magnetic resonance cholangiopancreatography in patients with suspected bile duct obstruction.

BACKGROUND: The value of magnetic resonance cholangiopancreatography (MRCP) is under debate. AIMS: To assess the diagnostic accuracy of MRCP and endoscopic retrograde cholangiopancreatography (ERCP) and to determine whether MRCP may help to prevent unnecessary interventional procedures. METHODS: Eighty six patients with suspected common bile duct obstruction who presented between January and December 1996 were enrolled. Twenty six were excluded due to anatomical reasons or because MRCP or ERCP could not be performed successfully. Results of MRCP were interpreted by two radiologists and a gastroenterologist unaware of clinical diagnosis. Final diagnosis was determined by ERCP and histopathological findings or a follow up of at least 12 months. RESULTS: MRCP images of diagnostic quality were obtained in all 60 patients. Thirteen patients had a clear bile duct. Sensitivity and specificity for the detection of any abnormality (n=47) were 89% and 92%, and for the detection of malignancy (n=27) 81% and 100%, respectively. These results were equivalent to the respective figures of ERCP (91% and 92% for any abnormality, and 93% and 94% for malignant diseases). CONCLUSIONS: MRCP is as sensitive as ERCP in the evaluation of bilary tract diseases. As the specificity of this non-invasive technique is close to 100%, MRCP may prevent inappropriate invasive explorations of the common bile duct and pancreatic duct.

Adolescent↗
PubMed1997

Value of magnetic-resonance cholangio-pancreatography (MRCP) after unsuccessful endoscopic-retrograde cholangio-pancreatography (ERCP).

BACKGROUND AND STUDY AIMS: The present study tries to evaluate the success rate of MRCP when two attempts by experts to perform ERCP in a center failed. PATIENTS AND METHODS: From March 1996 to December 1996 thirteen patients fulfilled the inclusion criteria. The MR cholangiopancreatograms were acquired using commercially available software in a clinical MR scanner (Magnetom Expert 1 T-Scanner, Siemens, Erlangen, Germany). MRCP utilized heavily T2-weighted turbo-spin echo sequences with fat supression (HASTE). Maximum intensity projection (MIP) of the pancreatic duct and biliary tree was then carried out. Additionally, T1-weighted sequences were obtained using the breath-hold technique. RESULTS: The MRCP images were of diagnostic quality in all 13 patients. In five cases the diagnoses detected by MRCP were followed by an interventional procedure. One patient showed a pancreatic pseudocyst, that was percutaneously drained using ultrasound guidance. In three cases we found benign bile duct obstruction, all of which were successfully treated by percutaneous transhepatic drainage. In one patient choledocholithiasis was diagnosed, the stone was successfully managed by percutaneous transhepatic extraction. CONCLUSION: MRCP is the method of choice in cases where ERCP is incomplete or where duct cannulation is not possible. A further advantage of MR imaging is the fact that it may provide complementary information about the whole region of interest, thus detecting the cause of duct pathology in many cases.

Aged↗
PubMed1997

Identification of active-site residues in protease 3C of hepatitis A virus by site-directed mutagenesis.

Picornavirus 3C proteases (3Cpro) are cysteine proteases related by amino acid sequence to trypsin-like serine proteases. Comparisons of 3Cpro of hepatitis A virus (HAV) to those of other picornaviruses have resulted in prediction of active-site residues: histidine at position 44 (H44), aspartic acid (D98), and cysteine (C172). To test whether these residues are key members of a putative catalytic triad, oligonucleotide-directed mutagenesis was targeted to 3Cpro in the context of natural polypeptide precursor P3. Autocatalytic processing of the polyprotein containing wild-type or variant 3Cpro was tested by in vivo expression of vaccinia virus-HAV chimeras in an animal cell-T7 hybrid system and by in vitro translation of corresponding RNAs. Comparison with proteins present in HAV-infected cells showed that both expression systems mimicked authentic polyprotein processing. Individual substitutions of H44 by tyrosine and of C172 by glycine or serine resulted in complete loss of the virus-specific proteolytic cascade. In contrast, a P3 polyprotein in which D98 was substituted by asparagine underwent only slightly delayed processing, while an additional substitution of valine (V47) by glycine within putative protein 3A caused a more pronounced loss of processing. Therefore, apparently H44 and C172 are active-site constituents whereas D98 is not. The results, furthermore, suggest that substitution of amino acid residues distant from polyprotein cleavage sites may reduce proteolytic activity, presumably by altering substrate conformation.

3C Viral Proteases↗
PubMed1996

[Infectious diseases: current diagnostic methods].

A microbiological diagnosis is either based on the direct detection of the pathogen or on the reaction of the host (indirect method). Many pathogens, in particular small bacteria and viruses, are undetectable by culture or difficult to cultivate. Molecular methods for the direct detection of such pathogens have been widely introduced in many microbiological laboratories within the past few years. The characteristics of these methods as well as new culture methods and new serological tests are discussed.

Bacteria↗
PubMed1996

Identification of hepatitis A virus non-structural protein 2B and its release by the major virus protease 3C.

The RNA genome of hepatitis A virus (HAV) encodes a giant polyprotein that is putatively cleaved proteolytically into four structural and seven non-structural proteins. So far, most of the proposed non-structural proteins and their respective cleavage sites have not been identified. A vaccinia virus recombinant (vRGORF) containing the complete HAV ORF under the control of the bacteriophage T7 promoter was used to express HAV in recombinant animal cells (BT7-H) that constitutively expressed T7 DNA-dependent RNA polymerase. A HAV-specific 27.5 kDa expression product was identified as peptide 2B. The 27.5 kDa 2B antigen was also found in HAV-infected MRC-5 cells. The N-terminal amino acid residues of the new peptide 2B are Ala-Lys-Ile-Ser-Leu-Phe and polyprotein cleavage between 2A and 2B occurred at amino acids 836-837 (Gln-Ala). Furthermore, heterologous expression in the same system of regions P1-P2 and of the protease 3C (3Cpro) gene, showed that P1-P2 polyprotein is not cleaved autocatalytically but by 3Cpro. Hence, 3Cpro is effective in cleaving the polyprotein 2A-2B junction.

3C Viral Proteases↗
PubMed1996

RNA-protein interactions at the 3' end of the hepatitis A virus RNA.

The regulative cis-acting terminal RNA structures and the proteins involved in the amplification of the hepatitis A virus (HAV) genome are unknown. By UV cross-linking/label transfer experiments, we have analyzed sequences of the 3'-nontranslated region (3'NTR) and preceding domains of the viral genome for their ability to interact with host proteins. A series of cDNA constructs were used to create genomic- and antigenomic-sense transcripts. The results show that the 3'-NTR-poly(A) interacted with host cell proteins with molecular masses of 38, 45, 57, 84, and 110 kDa only weakly, compared with RNA structures also consisting of 3D-coding regions. Protein p38 was most efficiently labeled after interaction with secondary-structure elements located at the 3' end of the HAV RNA, p38 also interacted with a 5'-terminal RNA probe. Optimal RNA binding was found to be dependent on the salt concentration. The specificity of the RNA-protein interaction was proven by competition assays. These data might indicate that a higher-order structure formed at the junction of the 3Dpol-coding sequence and the 3'-NTR of the HAV genome (putative RNA pseudoknot) significantly improves binding of host proteins and thus suggests that this structure might be essential for the formation of the replication complex initiating minus-strand RNA synthesis.

Animals↗