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Biomedical subjects

S Weber

Publications and source records attributed to S Weber.

At least 307 records · Page 17Linked to original sources
PubMed1985

Nifedipine and alpha 1-adrenergic blockade in Raynaud's phenomenon.

The efficacy of nifedipine and prazosin in the treatment of Raynaud's phenomenon was assessed in a prospective double-blind randomized cross-over trial in 15 patients. Each patient received one week of nifedipine 20 mg TID, one week of prazosin 1 mg TID, and 2 weeks of placebo. Nifedipine was shown to be effective in reducing both the frequency and the severity of Raynaud's phenomenon, whereas prazosin was ineffective. Before initiation of therapy in the 15 patients, pressor responses to the intravenous alpha 1-agonist phenylephrine were assessed in the basal state, 30 min after 20 mg oral nifedipine, and 30 min after 1 mg oral prazosin; the shift to the right of the log dose-vasopressor response curves to phenylephrine was similar with nifedipine and prazosin.

Adult↗
PubMed1985

Structure and biology of the globular domain of basement membrane type IV collagen.

A procedure was developed for purifying the globular domain NC1 of basement membrane collagen from collagenase digests of a variety of tissues. The globule (Mr = 170,000) is a hexameric structure originating from two collagen IV molecules that are cross-linked at their COOH-terminal ends. Dissociation into subunits derived from alpha 1(IV) and alpha 2(IV) chains occurs at a pH below 4 and after denaturation (8 M urea). The subunits obtained include monomers (Mr = 28,000) and two different dimers (Da,Db) which are connected by disulfide bonds (Db) and/or nonreducible bonds (Da). Almost perfect reconstitution to hexamers is obtained in neutral buffer with mixtures of the subunits or purified dimers but not with purified monomers. Stabilization by dimer formation and other physical data suggest conformationally distinct segments within the subunits, which is also supported by a repeating subdomain structure deduced from cDNA sequences. Monocline crystals of NC1 give a sufficiently detailed X-ray diffraction pattern that should permit elucidation of the three-dimensional structure of the hexamer. Antibodies raised against the globular domain react with all subunits and mainly recognize epitopes stabilized by internal disulfide bridges and/or the hexameric assembly. Immunoprecipitation tests with these antibodies demonstrated a slightly larger subunit size of NC1 in PYS-2 cell culture and the rapid release of precursor-specific segments prior to secretion from the cells. Autoantibodies against mouse tumor NC1 were produced in mice and were detected both in the blood and as tissue-bound forms (kidney, lung). The autoantibody response is accompanied by certain pathological alterations mimicking Goodpasture's syndrome. The possible relationship between the two diseases is substantiated by reaction of Goodpasture antisera with the globular domain obtained from various tissue sources.

Animals↗
PubMed1985

Gastrin releasing peptide is a selective mitogen for small cell lung carcinoma in vitro.

Human small cell lung carcinoma (SCLC) cells have been shown to contain significant levels of a bombesin-immunoreactive peptide. The 27-amino acid peptide, gastrin releasing peptide (GRP), has recently been shown to be responsible for the bombesin-like immunoreactivity found in SCLC cells. Among four lung cancer cell lines examined in vitro, GRP exhibited mitogenic activity for two SCLC subtypes, but not for a squamous carcinoma or adenocarcinoma lung cell line. The mitogenicity of the GRP molecule has been isolated to the carboxyterminal fragment, designated GRP 14-27, which is in part homologous to bombesin. The aminoterminal fragment, GRP 1-16, is no homologous to bombesin and exhibits no mitogenic activity. Thus, GRP may be an important growth regulating or autocrine factor in human SCLC.

Carcinoma, Small Cell↗
PubMed1985

[Monoclonal antibodies and their potential application to medicine].

Monoclonal antibodies have been increasingly applied in medicine for diagnostic and therapeutic purposes instead of conventional antisera. In addition to their unlimited availability monoclonal antibodies have the advantage of defined specificity, affinity and of standard parameters. This paper describes the production of monoclonal antibodies using the hybridoma technique and surveys some potential fields of application such as infections, transplantations, tumours and lung diseases.

Antibodies, Monoclonal↗
PubMed1985

Prevention with molsidomine of coronary artery spasm caused by alkalosis.

A provocative test of coronary artery spasm caused by alkalosis was used to evaluate a possible anti-coronary artery spasm effect of molsidomine. The rapid infusion of an alkaline buffer followed by maximal voluntary hyperventilation in 10 patients with angina at rest led to the appearance of anginal pain and significant, transient ischemic changes of the ST segment resulting from alkalosis-induced coronary spasm. A second provocative test was performed under the same conditions, 24 hours later, after the administration of 4 mg of molsidomine. Molsidomine prevented the development of coronary artery spasm in 8 of the 10 patients in the study group. These preliminary results justify further clinical evaluation of molsidomine in the treatment of vasospastic angina.

Alkalosis↗
PubMed1985

[Classification and principles of the use of vasodilators in the treatment of left ventricular insufficiency].

Vasodilators have been widely used in recent years for the treatment of severe left ventricular failure (LVF). However, amongst these drugs, not all have the same therapeutic effects, but they differ from one another in molecular structures, cellular mechanisms, haemodynamic actions and modes of administration. A three tier classification is proposed with the single objective of facilitating the therapeutic choice: mechanism of action: this property distinguishes the alpha-blockers from the beta-2 sympathomimetics, calcium antagonists, angiotensin converting enzyme inhibitors and prostacyclin biosynthesis inducers. Some molecules such as hydralazine, whose mechanism of action remains unclear, cannot be classified in this way; haemodynamic effects: these effects can be used to distinguish vasodilators which act mainly on the venous sector from arterial and mixed vasodilators. The knowledge of the preferential site ol action of these molecules helps to adapt the choice of treatment to the initial haemodynamic profile of each patient; pharmacokinetics: these properties distinguish molecules active only by intravenous administration, better adapted for the treatment of acute LVF in the intensive care unit, from those active orally which can be used for long-term ambulatory therapy of chronic cardiac failure. Trinitrin and its derivatives occupy an intermediate position because of their relatively low bioavailability after oral administration: long-term administration is not always easy and may require special modes of administration (i.e. percutaneous). Vasodilators have been widely used in cardiac failure for about 5 years; the results of some medium term controlled therapeutic trials are now available and confirm the efficacy of these drugs but also define their limitations: variable therapeutic efficacy: the number of responders ranges from 30 to 60 p. 100 according to the molecule used.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗
PubMed1984

Subunit structure and assembly of the globular domain of basement-membrane collagen type IV.

The globular domain of collagen IV was solubilized by collagenase digestion from a mouse tumor, human placenta and bovine aorta and was purified by chromatographic methods. The materials show a unique, mainly non-collagenous amino acid composition and contain small amounts of glucosamine and galactosamine. The globular structures with Mr = 170 000 appear as a hexameric assembly originating from two collagen IV molecules. Subunits of this assembly are two different dimers Da and Db (Mr about 56 000) and monomers (Mr = 28 000). Their N-terminal amino acid sequences start with short triple-helical sequences, which overlap with the C-terminal triple helix of the alpha 1(IV) and alpha 2(IV) chain, demonstrating that the globule originates from the C terminus of collagen IV. Dimers arise from monomers by disulfide cross-linking (form Db) and/or formation of non-reducible cross-links (form Da). Reduction under non-denaturing conditions causes partial dissociation of the globule and of collagen IV dimers, indicating that reducible cross-links are formed between monomers of two different collagen IV molecules. Dissociation of the hexamer into the subunits can be achieved with 8 M urea, sodium dodecyl sulfate or in the pH range 2.5-4. The latter indicates that carboxyl groups are essential for association. Mixtures of the subunits (monomers and dimers) or purified dimers reassemble in neutral buffer into hexamers as shown by ultracentrifugation and electron microscopy. Reconstituted hexamers, however, dissociate in a much broader pH range than the native globules. Circular dichroic spectra indicate that the structure is more completely refolded from acid-treated than from urea-treated material. These data suggest that globules originating from monomers (as existing in single collagen IV molecules) are stabilized by the adjacent triple helix. Covalent cross-link formation stabilizes the globular structure and allows reconstitution in stoichiometric proportions.

Animals↗
PubMed1984

Laminin, proteoglycan, nidogen and collagen IV: structural models and molecular interactions.

Major components of basement membranes, including collagen IV, laminin, heparan sulphate proteoglycan and nidogen, were isolated from the matrix of the EHS sarcoma. The purified components were analysed for their domain structure and for the participation of distinct domains in molecular interactions and cell binding. Collagen IV consists of four domains which have triple helical or non-collagenous structures. Self-assembly of the protein into a network-like organization occurs by specific interactions between N-terminal triple helical segments and between the C-terminal globules. Cell binding requires a central triple helical segment. Laminin has the shape of an asymmetrical cross; different globular domains within this structure mediate binding to proteoglycan and to cells. The proteoglycan consists of four heparan sulphate chains attached to a small protein core. These chains have the potential to bind laminin, fibronectin and collagen IV. Nidogen was isolated in several molecular forms which showed either self-aggregation or binding to laminin.

Animals↗
PubMed1984

Ultrasonographic diagnosis of brain tumors in infancy.

Fourteen intracranial tumors were diagnosed by means of mechanical sector scanning through the infant's open fontanelle in a series consisting of 1150 examinations. In addition, integrated pulsed Doppler-sonography (duplex-scan technique) was used to diagnose malformations of intracranial vessels. We established five diagnostic criteria: high echogenic structures are mostly seen in solid tumors of the periventricular region; low echogenic structures are seen in infiltrating tumors of the cerebral tissue and they are difficult to recognize; echo-free structures correspond with a cystic process, a necrosis or malformation of vessels; indirect sonographic signs of a cerebral tumor are all changes in shape and size of the normal anatomic structures; and abnormal blood-perfusion of a marked region, e.g. caused by dilatations of vessels, can be proved by integrated pulsed Doppler-sonography.

Brain Neoplasms↗
PubMed1984

[Use of beta-blockers in the acute phase of myocardial infarction].

Several experimental studies have demonstrated that the early administration of beta blockers in the setting of an acute myocardial infarction (in the first six hours) tended to diminish the area of myocardial necrosis. Numerous attempts to limit infarct size with beta blockers have occurred over the past ten years. Without a reliable and reproducible method to measure necrosed tissue, it has been difficult to evaluate the effectiveness of this therapy. Presently available studies have demonstrated, however, that beta blockers are well tolerated in the setting of an acute infarction as long as none of the usual contraindications are present. The majority (but not all) of these studies indicated improvement in parameters used to determine the amount of tissue necrosis and a tendency (not always significant due to the small numbers studied) to decrease morbidity and mortality during hospitalization. One study using metoprolol administered during the acute phase and continued during the first three months demonstrated a significant decrease in mortality. The results of this study are very demonstrative, nevertheless, once the acute necrotic phase is over, it is difficult to ascertain whether diminished tissue necrosis or the preventive effect of beta blockers is responsible for these findings until a recurrence or sudden death occurs.

Adrenergic beta-Antagonists↗
PubMed1983

[Multisegmental dynamic plethysmography for noninvasive study of venous function with special reference to exercise hyperemia].

Multilevel dynamic strain gauge plethysmography was evaluated in 22 healthy subjects. Venous volume changes were measured at the foot and calf level during tip-toeing exercise and at the thigh level during kneebends. These normal data were compared to those in 26 patients with chronic venous incompetence (CVI). Two types of curve resulted in the healthy subjects: if sensing site and exercised musculature do not correspond (foot sensing and calf-muscle exercise), venous volume decreases during exercise and stays on a constant level. However, if sensing site and exercised muscles are identical (calf--tip-toeings; thigh--kneebendings), venous volume increases again during exercise after a maximum volume decrease. This could be quantified by the volume increase angle beta. These mechanisms can be explained by exercise hyperemia. In patients suffering from CVI with only partially recanalized thrombotic occlusions, venous drainage is not sufficient and results in a significantly reduced (p less than 0.001) decrease in venous volume during exercise at the calf, or even in a volume increase. In the foot segment examined, however, no significant differences were found. Additional measurements at the thigh level are recommended for patients with a history of iliac vein thrombosis, especially for objective evaluation of intermittent venous claudication.

Adult↗