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Biomedical subjects

R Wüthrich

Publications and source records attributed to R Wüthrich.

At least 19 recordsLinked to original sources
PubMed1999

1,25-dihydroxyvitamin D3 stimulates transforming growth factor-beta1 synthesis by mouse renal proximal tubular cells.

1,25-dihydroxyvitamin D3 [1,25-(OH)2 D3] is a secosteroid hormone with effects on cell growth, differentiation and immunoregulatory functions in a number of tissues not primarily involved in mineral metabolism. We recently demonstrated growth-regulating effects of 1, 25-(OH)2 D3 on human mesangial cells and proximal tubular cells. To investigate whether 1,25-(OH)2 D3 might also affect the synthesis of cytokines and growth factors in proximal tubular cells, we assessed in the present study the expression and secretion of transforming growth factor-beta1 (TGF-beta1) in a mouse proximal tubular cell line (MCT) in vitro. TGF-beta1 synthesis was measured by a monospecific ELISA in culture supernatant. The secreted TGF-beta1 was proven to be biologically active by means of a bioassay system (CCL-64 mink lung epithelial cell proliferation assay). TGF-beta1 gene expression was assessed by RT-PCR. To analyze whether TGF-beta1 expression mediates the 1,25-(OH)2 D3-induced antiproliferative actions in MCT, proliferation studies in the absence or presence of a blocking monoclonal anti TGF-beta1-3 antibody were performed. 1, 25-(OH)2 D3 (10(-11) to 10(-7) M) specifically increased the TGF-beta1 protein secretion in MCT with a maximum at 10(-8) M. No detectable effect was found with 25 D3 at 10 times higher concentrations. A synthetic 20-epi analogue, MC 1288, increased TGF-beta1 secretion up to similar amounts at equimolar concentrations as the natural hormone 1,25-(OH)2 D3. Steady-state TGF-beta1 mRNA concentration in MCT was transiently increased by 1, 25-(OH)2 D3 between 12 and 24 h, returning to control values at 48 h. Blocking TGF-beta1 did not reduce or abrogate the antiproliferative effect of 1,25-(OH)2 D3. In conclusion, 1,25-(OH)2 D3 stimulates TGF-beta1 expression in renal proximal tubular cells, a growth factor with anti-inflammatory and profibrotic actions which plays an important role in the development and progression of nephrosclerosis.

Animals↗
PubMed1993

[Antibiotic-resistant pneumonia].

A 77-year-old lady with malaise, cough, weight loss, an elevated ESR and bilateral patchy infiltrates on the chest X-ray is described. The symptoms progressed inspite of antibiotic treatment. On the basis of clinical findings, transbronchial biopsy, bronchoalveolar lavage and lung function tests the diagnosis of a bronchiolitis obliterans, organizing pneumonia (BOOP) was established. The clinicopathological entity of BOOP, its differential diagnosis and treatment are discussed.

Aged↗
PubMed1993

[Febrile status and micronodular changes of the lung parenchyma in HIV infection].

This 49-year-old man with the acquired immunodeficiency syndrome (AIDS) was admitted to the hospital because of fever, weight loss and respiratory symptoms. The radiograph of the chest showed diffuse fine nodular opacities. Histology of lung and lymph node revealed a necrotising granulomatosis and yeasts suggesting histoplasmosis. It's identity was confirmed by positive cultures for Histoplasma capsulatum in blood, urine, lung specimen and lymph node. There was a successful induction treatment and a maintenance therapy with amphotericin B. We discuss disseminated histoplasmosis in the immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗
PubMed1992

[Multiple sclerosis in northwestern Switzerland].

From 1980 to 1987 an epidemiologic survey was conducted in northwestern Switzerland (population 523,000) with the aim of registering as many MS cases as possible. The prevalence for the entire region was 142 per 100,000, with a maximum of 164/100,000 in the city of Basle. Extrapolation suggests there are more than 8000 MS patients living in Switzerland. Other interesting results were: a sex-ratio of 2.2 females:1 male. The mean age at clinical onset was 31.6 years. The mean survival was 30.6 years. Prevalence has grown in recent decades, mainly due to longer survival and to changes in age structure. The incidence presumably remained unchanged.

Adult↗
PubMed1991

Nonionic polyethylene glycol-ferrioxamine as a renal magnetic resonance contrast agent.

The MR relaxation properties of ferrioxamine-B, a chelate of iron, were investigated in vitro and in vivo to establish the potential use of the compound as a paramagnetic contrast agent. Whereas the paramagnetic relaxivity of ferrioxamine-B is such that, compared to gadolinium-DTPA (Gd-DTPA), two to three times higher concentrations are necessary to produce the same relaxation effects, the toxicity of the iron ion should be much lower because of the availability of physiological metabolic pathways. Preliminary experiments in three dogs under invasive cardiovascular monitoring demonstrated that high-dose bolus application (0.1-0.3 mmol/kg body weight) of ferrioxamine-B leads to a precipitous blood pressure drop to almost zero, lasting for several minutes. This reaction seems most likely the result of a negative inotropic effect of ferrioxamine-B. In order to reduce these side effects ferrioxamine was modified to a nonionic derivative, PEG-ferrioxamine-B. In vivo experiments with this compound did not demonstrate any substantial change in blood pressure. Dynamic MR imaging of the kidneys and the liver was performed after bolus injection of the compound in six dogs. The results indicate that PEG-ferrioxamine-B produces effects very similar to Gd-DTPA, resulting in T1-mediated signal intensity increases in the liver and in the early stages of passage through the kidneys. During the phase of medullary concentration, T2 effects seem to dominate visualization of the renal medulla. The nonionic PEG-ferrioxamine-B derivative appears to offer an alternative to gadolinium-containing chelates as an MR contrast agent.

Animals↗
PubMed1990

MRI signal loss due to microcirculation: phantom studies.

In order to study perfusion effects in MRI under different conditions we developed two different kinds of phantoms. The first phantom exhibits linear capillary flow with several capillaries within one voxel. The second consists of an anion exchange resin with beads forcing the spins to change directions such that they undergo accelerations and decelerations. Both phantoms were imaged with standard spin-echo sequences and signal intensities were quantified at various echo times. Qualitative and quantitative agreements of the data with the results obtained by computations of signal loss due to spin-phase phenomena are excellent, thus suggesting that perfusion effects can be fully understood using these phenomena. It is argued that the phantoms used in conjunction with conventional spin-echo sequences represent a realistic model for studying true capillary networks in conjunction with specialized perfusion sequences.

Humans↗
PubMed1990

A pharmacokinetic and MRI study of unilamellar gadolinium-, manganese-, and iron-DTPA-stearate liposomes as organ-specific contrast agents.

Small unilamellar liposomes that contain the lipophilic chelate DTPA-stearate (DTPASA) were used as carriers for the paramagnetic metal ions gadolinium, manganese, and iron. The iron liposomes were unstable in vitro and thus not studied further. The natural targeting properties of these liposomes to the reticuloendothelial system was used in rats and dogs for the imaging of liver and spleen. In vitro incubations with human plasma, followed by high-pressure liquid chromatography (HPLC) separation of the Gd-DTPASA and Mn-DTPASA liposomes showed that after an incubation period of 24 hours, only 4% of the gadolinium was bound to the plasma proteins, whereas, with the Mn-DTPASA liposomes, a transfer of 40% manganese was seen. These results indicate that the Mn-DTPASA complex is not stable. On T1-weighted images, both liposome preparations gave a strong signal enhancement of the organs of the mononuclear phagocyte system (MPS). Gadolinium liposomes accumulated in the liver of rats at a peak concentration 4 hours after application and at a higher concentration compared with the manganese liposomes. Gd-DTPASA liposomes had an elimination half-time from the liver of 61 hours. Manganese liposomes produced stronger contrast at lower concentrations and had faster elimination kinetics from the liver, with a major elimination half-time of 10 hours. Both chelate complexes were eliminated predominantly by the hepatobiliary route. Thus, liposomal Gd-DTPASA appears to be a stable, efficient, and specific magnetic resonance imaging (MRI) contrast agent for the upper abdomen.

Animals↗
PubMed1989

[MRI and the diagnosis of multiple sclerosis].

88 patients aged 22-70 (mean 44) years, presenting with symptoms and/or signs of multiple sclerosis, were investigated by MRI for the purpose of revealing MS-like lesions. 54% of all patients had MRI scans suggestive of MS. Patients with clinically definite MS had MS-suggestive lesions in 85% of cases, and none was normal. In patients with possible signs or symptoms of MS the rate of MS-suggestive MRI scans was 34%. MS lesions can be detected, in decreasing order, in the white matter of the hemispheres (centra semiovalia), the periventricular system, the basal ganglia and the posterior fossa. MRI confirms the diagnosis of clinically definite MS and diagnoses MS in cases with questionable MS symptoms or signs.

Adult↗
PubMed1988

[Isoelectric focusing in neurological diagnosis].

The cerebrospinal fluid (CSF) of 1673 neurological patients in whom conventional agar electrophoresis failed to provide conclusive results was analyzed by isoelectric focusing (IEF). The primary aim of the study was not to analyze the frequency of oligoclonal immunoglobulins in the CSF of patients with inflammatory diseases of the central nervous system (CNS) but to answer the question how often, and in which particular disturbances, gamma-globulin changes typical of inflammatory processes are found in conditions which do not primarily belong to the group of inflammatory CNS diseases. It is shown that oligoclonal IgG bands in these circumstances are not common but did occasionally occur in most diagnostic groups. Results suggest increased frequency in certain groups such as Guillain-Barré polyradiculitis and in various neoplastic disorders. The diagnostic difficulties resulting from these findings and the advantages of IEF over the more generally favoured "Ig-index" are discussed. In addition, we report on the occasional appearance of monoclonal IgG gammopathies either associated with inflammatory CNS reactions or - more frequently - as an isolated and unexplained finding.

Central Nervous System Diseases↗
PubMed1986

Effects of atrial natriuretic peptide on the stimulation by angiotensin II of various target cells.

The effects of the synthetic (1-24) atrial natriuretic peptide (atriopeptin III) on angiotensin II-induced changes in cytosolic free calcium and biological responses have been examined in three cell types: adrenal glomerulosa cells, vascular smooth muscle cells and renal cortical tubular cells. Atriopeptin III did not affect the transient changes in cytosolic free calcium induced by angiotensin II in adrenal glomerulosa and vascular smooth muscle cells, nor did it alter resting cytosolic free calcium levels. In contrast with its known inhibitory effects on angiotensin II-induced aldosterone production and vasoconstriction, atriopeptin III did not prevent either angiotensin II-stimulated prostaglandin 6-keto-F1 alpha or prostaglandin E2 (PGE2) synthesis in cultured vascular smooth muscle cells and dispersed renal cortical tubular cells, respectively. These data show that atrial natriuretic peptide is not an endogenous calcium-blocking agent, and indicate that the atrial peptide is not a general inhibitor of all angiotensin II-induced biological responses.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Inefficacy of the commercial live oral Ty 21a vaccine in the prevention of typhoid fever.

The efficacy of the live oral typhoid fever vaccine Ty 21a marketed in Switzerland in 1981 was investigated. Forty-seven Swiss travellers to Third World countries contracted typhoid fever in 1982 and 1983; 20 (43%) of these persons had been vaccinated with Ty 21a. The incidence of typhoid fever in vaccinees was 1.1 per 10,000 doses of Ty 21a vaccine sold, which was similar to the incidence of 0.9 per 10,000 doses for the ineffective killed Ty 2 vaccine. Comparison of the incidence of vaccination in patients with typhoid fever in 1983 and in healthy travellers to India revealed vaccination efficacy rates which were not significantly different from zero. It is suggested that Ty 21a vaccine in the form marketed in Switzerland in 1981-1983 is not sufficiently potent or heat-stable, so that the doses of viable bacteria ingested were too low.

Administration, Oral↗
PubMed1977

Computerized transverse axial tomography (CTAT) in the diagnosis of epilepsy.

99 patients with late epilepsy were investigated in our EEG laboratory. In intervals of maximal 100 days (averaged 23 days) a waking EEG recording and a CTAT were carried out. The average age was 43. 62.5% of the pathological CTATs were found in partial seizures with elementary symptomatology. In patients with generalized seizures the diagnosis of symptomatic epilepsy could be made in 20 cases (34%) with the help of computerized tomography. Generalized seizures were related to tumors only in 8.5% in our case material. In 20 of 99 EEGs in our patients there was a continuous delta wave focus, 12 of these with epileptogenic activity. Of these 20 patients, 18 showed a pathological result in computerized tomography. Eight tumors or metastases, 8 cases of atrophy (7 local and 1 diffuse) as well as 1 case of encephalitis could be diagnosed. 12 EEGs showed continuous or intermittent theta wave foci. Computerized tomography never gave a pathological finding in these patients. If one compares the results of CTAT and EEG in cases of tumor, the agreement between positive tomography and the pathological EEG is very high (97%): 33 positive CTATs comapred with 31 positive EEGs. Our investigations with computerized tomography show organic findings in 34 of 99 epilepsies, that is about 34%.

Adolescent↗
PubMed1977

The course of multiple sclerosis cases with extremely high gamma-globulin values in the cerebrospinal fluid.

40 selected cases of multiple sclerosis (MS) with extremely high gamma-globulin values in the cerebrospinal fluid (CSF) (over 25 rel%, upper normal limit 7.5 rel%) were matched with the same number of MS patients with normal CSF findings. Surprisingly, no definite relationship could be shown between the amount of CSF gamma-globulins and the various clinical criteria in MS, such as age, type of progression, duration of illness, remission, extent of plaques and gravity of the disease.

Adolescent↗