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Biomedical subjects

M Alberts

Publications and source records attributed to M Alberts.

At least 37 records · Page 2Linked to original sources
PubMed1992

Sequence and molecular characterization of human monocyte/neutrophil elastase inhibitor.

cDNA encoding human monocyte/neutrophil elastase inhibitor (EI), a M(r) approximately 42,000 protein with serpin-like functional properties, has been sequenced. The 1316-base-pair sequence was obtained from overlapping clones and amplified DNA from libraries of monocyte-like and neutrophil-like cells. Hybridization with EI cDNA identified three EI mRNA species of 1.5, 1.9, and 2.6 kilobases in U937 monocyte-like cells and no hybridizing mRNA in lymphoblastoid cells lacking detectable EI. The cDNA open reading frame encodes a 379-amino acid protein, of which 167 residues were confirmed by tryptic peptides. Although EI may function extracellularly as well as intracellularly, its deduced sequence lacks a typical cleavable N-terminal signal sequence. Sequence analysis established that EI is a member of the serpin superfamily. EI has greatest homology (50.1% identity of amino acids) with plasminogen activator inhibitor 2, also a monocyte protein, and ovalbumin and gene Y, which were previously grouped as an ancient branch of the serpin superfamily. The extent of EI identity with the functionally related serpin alpha 1 antitrypsin is only 30.1%. Sequence alignment indicates that the reactive center P1 residue is Cys-344, consistent with abrogation of elastase inhibitory activity by iodoacetamide and making EI a naturally occurring Cys-serpin. The cleavable bond, Cys-Met, suggests an oxidation-sensitive molecule capable of inhibiting more than one serine protease. Oxidation sensitivity would limit the place of action of EI to the immediate vicinity of carrier cells. The molecular structure will help clarify the likely role of EI in regulating protease action and preventing tissue damage by phagocytic cells.

Amino Acid Sequence↗
PubMed1990

Large-dose infusions of heparinoid ORG 10172 in ischemic stroke.

We evaluated the safety and possible efficacy of large doses of the heparinoid ORG 10172 in 57 patients with acute or progressing ischemic stroke. Patients received a loading bolus of the drug followed by a maintenance intravenous infusion for 7 days. The plasma level of ORG 10172 was monitored by the degree of inhibition of coagulation factor Xa. In general, the drug was well tolerated and few hemorrhagic complications occurred. Two patients with large cardioembolic hemispheric strokes had intracranial hemorrhagic complications. Most patients improved during treatment. By 3 months after the stroke, 37 patients (65%) had a favorable outcome (minimal or no residual disability). This study suggests that high-dose intravenous infusions of ORG 10172 can be safely given to patients with acute ischemic stroke.

Adolescent↗
PubMed1989

A dose escalation study of ORG 10172 (low molecular weight heparinoid) in stroke.

An intravenous infusion of a low molecular weight heparinoid, with a reduced risk of hemorrhage, may be an alternative to heparin in the management of acute ischemic stroke. To evaluate this hypothesis, we studied the safety of the heparinoid, ORG 10172, in a dose-escalation study in 26 patients. The drug was administered as a loading bolus followed by a 7-day infusion in five rates with target anti-factor Xa levels from 0.2 to 1.0 U/ml. The drug was well tolerated; no major bleeding complications or thrombocytopenia occurred. There were no deaths or hemorrhagic transformation of cerebral infarctions. The results indicate that ORG 10172 at doses to achieve a level of 1.0 U/ml or less may be used safely in management of acute cerebral infarction.

Adult↗
PubMed1987

Effects of gluconeogenic hormones on insulin binding in intact human red blood cells.

The effects of gluconeogenic hormones, adrenaline and cortisol, on insulin binding were studied in intact human red blood cells. Insulin binding was significantly decreased when red blood cells were preincubated with 1.0 microgram . ml-1 adrenaline or cortisol respectively. The Scatchard plot suggested that this was due to a decrease in surface receptor concentration. Furthermore, it showed that adrenaline also increased insulin receptor affinity. The negative co-operativity affinity profile demonstrated that adrenaline caused a rise in only the upper limit average affinity, Ki, of the insulin receptor.

Epinephrine↗
PubMed1987

Monoclonal antibodies to the extracellular glucosyltransferases from Streptococcus sobrinus 6715.

Murine monoclonal antibodies (MAbs) were raised against the glucosyltransferases (GTFs) of Streptococcus sobrinus 6715. The antibody panels included MAbs raised against the primer-independent, soluble product enzyme (GTF-Si) which did not cross-react with other GTFs, as well as MAbs raised against the primer-dependent, soluble product enzyme (GTF-Sd) which recognized both GTF-Si and GTF-Sd, thus indicating that these catalytically distinct enzymes share epitopes. MAbs raised against GTF-I recognized several forms of GTF-I and did not cross-react with the GTF-S enzymes. None of the MAbs recognized the major glucan-binding protein of S. sobrinus. Two MAbs inhibited glucan synthesis, one blocking primer synthesis by GTF-Si by 89% and the second inhibiting that by GTF-I by 92%.

Antibodies, Bacterial↗
PubMed1981

Typhoid fever in the Northern Transvaal national states. An approach to an epidemiological quandary.

The serious nature of the high incidence rate of typhoid fever in the Northern Transvaal national states is discussed. It is recommended that epidemic areas be chosen as models to identify modes of transmission from carrier and other sources. In the endemic areas this approach is considered to be of limited value owing to geographical and social conditions. Education of the populace in basic hygiene at the primary and secondary school levels, followed by improvement in the health services and vaccination programmes, is recommended as suitable for reducing the incidence of the disease until potable water supplies and sewage disposal facilities can be provided.

Adolescent↗
PubMed1981

The Widal test in the diagnosis of typhoid fever in the transvaal.

We analysed the results of the Widal test in the northern and eastern Transvaal in relation to bacteriologically confirmed cases of typhoid fever, patients suspected of having the disease, febrile patients without typhoid fever and healthy individuals. Titres of 1:200 or greater for either H or O agglutinins were recorded for 75,2% of patients with bacteriologically proven typhoid fever, 4,6% of healthy subjects residing in an endemic area and 7,5% of patients presenting with non-thyroid fevers. Age, sex and region were found to affect the percentage of positive tests recorded. Despite these failings, the Widal test was found to be of value in the diagnosis of typhoid fever. The concept of a diagnostic titre was considered unreliable, but considered in conjunction with the clinical picture, O or H agglutinin titres of 1:200 or more may be regarded as strong presumptive evidence of typhoid fever.

Adolescent↗