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Biomedical subjects

D T Brown

Publications and source records attributed to D T Brown.

At least 145 records · Page 8Linked to original sources
PubMed1982

Monoclonal antibodies against two human lung carcinoma cell lines.

Monoclonal antibodies against 2 human lung carcinoma cell lines (E14 and BEN) were prepared by production and cloning of somatic cell hybrids between the murine myeloma NS1, and spleens from E14- and BEN-immune BALB/c mice. Approximately 2000 hybrid culture supernatants were screened for antibody simultaneously against the immunizing cell line and lung fibroblasts (573 Lu) using a radiolabelled Protein A binding assay. Although the vast majority secreted antibodies which recognized species-specific antigens, a few supernatants showed marked differential reactivity against E14 or BEN. These were cloned and subsequently tested against a panel of up to 25 human cell lines originating from different neoplastic and non-neoplastic tissues. Two anti-E14 clones (3E19.8 and 4EAB3.7) displayed preferential activity against lung cancer cell lines, but a low level of reactivity was also detectable with cell lines of different tissue provenance. The antibodies of 3 anti-BEN clones (7B3.5, 7B5.4, 7B17.7) likewise recognized antigens present to a higher density on lung cancer cell lines but were also reactive (to a variable extent for the different clones) with a diversity of other tumour cell lines. The antibodies of 2 further clones were exceptional in so far as one (7BC9.1) reacted only with BEN and WIDR (colorectal cancer) cells, while another (7B24.4) reacted, with apparent exclusivity, against BEN cells. With the exception of the latter, the distinction in antigen expression between many of the cell lines was quantitative rather than qualitative and the emergent picture is one of random expression of individual determinants on several disparate types of cancer cells, rather than restriction to cells of a given morphological type or histogenic derivation.

Antibodies, Monoclonal↗
PubMed1982

Penicillin-induced unstable intracellular formation of spheroplasts by rickettsiae.

Penicillin G (greater than or equal to 20 micrograms/ml) is rapidly rickettsiacidal for intracellular Rickettsia prowazekii. Light and electron microscopic examinations revealed that penicillin G in culture medium induced a predictable transformation into typical enlarging spheroplasts deficient in the internal, putative peptidoglycan layer of the outer membrane. Under certain conditions, spheroplasts ruptured to discharge contents into host cell cytoplasm and to leave empty shells of defective outer membrane and diffuse amorphous intracytoplasmic antigen. Host cell destruction often accompanied spheroplast rupture. Penicillin G (100 micrograms/ml) caused similar spheroplast formation by Rickettsia rickettsii, but 1,000 micrograms/ml caused neither growth inhibition nor spheroplast formation in Rickettsia tsutsugamushi. The clinical and epidemiological significance of a practical rickettsiacidal drug for the treatment of louse-borne typhus fever is discussed. Practical pharmacologic considerations preclude the use of penicillin for the treatment of typhus or spotted fever.

Animals↗
PubMed1982

Inhibition of Sindbis virus maturation after treatment of infected cells with trypsin.

Brief treatment of Sindbis virus-infected BHK-21 or Vero cells with low concentrations of trypsin irreversibly blocked further production of progeny virions after removal of the enzyme. The inhibitory effects of the trypsin treatment could only be demonstrated in cells in which virus infection was established; optimal inhibition occurred at ca. 3 h postinfection. Production of virus structural proteins PE2, E1, and C occurred at normal levels in inhibited cells. PE2 and E1 were also transported to the cell plasma membrane during inhibition; however, PE2 was not cleaved to E2, and little capsid protein became membrane associated relative to control cells. Although trypsin treatment had no effect on Sindbis protein synthesis, the production of both 26S and 42S RNA was greatly reduced. Similar trypsin treatment of BHK cells infected with vesicular stomatitis virus had no detectable effect on the course of virus infection.

Animals↗
PubMed1982

Pulmonary and systemic vascular actions of tolazoline in anesthetized dogs.

The cardiovascular actions of tolazoline are poorly understood. Therefore, we administered tolazoline (2 mg kg-1, IV) to anesthetized adult dogs and puppies. Tolazoline induced transient pulmonary and systemic pressor responses, transient systemic vasoconstriction and pulmonary vasodilation, and transient hypoxemia and acidosis in pentobarbital anesthetized dogs. None of these responses were evident during a second injection of tolazoline, indicating either the development of tachyphylaxis or a secondary antagonistic property of tolazoline. These responses to tolazoline were also prevented by alpha adrenergic blockade. Histamine H1 - and H2-receptor blockade sustained the transient pulmonary and systemic pressor and systemic vasoconstrictor responses to tolazoline. Thus, tolazoline appears to activate both alpha and histamine receptors in the pulmonary and systemic vascular beds of the anesthetized dog. In anesthetized puppies, tolazoline induced a slight pulmonary pressor response, marked bradycardia, and systemic hypertension. The present findings confirm the pharmacological complexity of tolazoline and suggest that anesthesia, age, and pulmonary vascular tone are important factors in determining the cardiovascular responses to tolazoline.

Anesthesia↗
PubMed1981

Adverse responses to i.v. anaesthetics.

The adverse reactions to i.v. anaesthetics which occurred during a 3-yr period in one hospital were investigated. Sixteen reactions were reported; 13 of these occurred in a total of 7906 administrations of Althesin, two in 45 546 administrations of thiopentone and one in 630 administrations of methohexitone. The pathological process was identified in 10 patients. Most reactions were caused by activation of the alternate pathway for complement conversion.

Adolescent↗
PubMed1981

Effects of posture on the spread of isobaric and hyperbaric amethocaine.

The effects of posture on the spread of isobaric and hyperbaric amethocaine were studied after intrathecal injection in 60 patients. Gravity had no effect on the spread of isobaric solutions and, while hyperbaric solutions did spread under the effect of gravity, it was found that posture could not be used to control spread effectively. The results also show that the dose of local anaesthetic injected had a more important effect on the duration of blockade than on the spread.

Anesthesia, Spinal↗
PubMed1981

Allergic reaction to an amide local anaesthetic.

A 67-yr-old female patient gave a history of allergy to lignocaine. When she was challenge-tested with the intradermal injection of 0.5% bupivacaine 0.2ml she had a systemic reaction. This reaction was accompanied by a decrease in the concentration of complement C4 in the plasma, which indicated that the reaction was immunologically-mediated. This is the first report of allergy to a local anaesthetic drug which has been documented by concurrent immunological changes.

Aged↗
PubMed1981

Alternate mechanism for amino acid entry into Neurospora crassa: extracellular deamination and subsequent keto acid transport.

The growth of the pm nbg mutant strain of Neurospora crassa was inhibited by the amino acid analog para-fluorophenylalanine despite the fact that none of the three constitutive amino acid permeases is functional in this strain. This observation led to the detection of both a deaminase which was released into the growth medium in response to para-fluorophenylalanine and a keto acid transport system which allowed entry of the resulting keto acid into the cell. The transported keto acid was recovered in cellular protein, suggesting its regeneration as the amino acid. The cooperative activity of these two systems represents an additional mechanism for the intracellular accumulation of amino acids, which is distinct from the known amino acid permeases.

Amino Acids↗
PubMed1981

Effects of chloroquine and cytochalasin B on the infection of cells by Sindbis virus and vesicular stomatitis virus.

The effects of cytochalasin B and chloroquine on the process of endocytosis of Sindbis virus particles and polystyrene spheres were determined by electron microscopy. The effects of these agents on the process of infection (attachment, penetration, and uncoating) of BHK-21 cells by Sindbis virus and vesicular stomatitis virus were also determined. Cytochalasin B completely blocked ingestion of Sindbis virus particles or latex spheres by BHK cells but had no effect on the ability of Sindbis virus or vesicular stomatitis virus to infect or replicate in BHK cells. Chloroquine did not inhibit the ingestion of either latex spheres or virus particles but greatly reduced the yields of virus produced. These data suggest that endocytosis is not essential for the infection of cultured cells by Sindbis virus or vesicular stomatitis virus.

Animals↗
PubMed1981

Isolation and partial characterization of a rheologically active glycoprotein fraction from pooled human sputum.

A rheologically active mucin fraction was isolated from pooled sputum and was shown to be free of any major protein contaminants. The procedure used allows the isolation to be carried out by a batch process so that sufficient material is available for extensive biochemical and biophysical studies. Because the separation was carried out using sputum, the purified material should prove suitable for the evaluation of drugs used in chronic obstructive airway disease. This paper describes the separation process in detail and the partial biochemical characterization of the mucin fraction.

Amino Acids↗
PubMed1980

Distribution of virus structural proteins and protein-protein interactions in plasma membrane of baby hamster kidney cells infected with Sindbis or vesicular stomatitis virus.

The plasma membrane of baby hamster kidney (BHK-21) cells infected with either Sindbis or vesicular stomatitis virus was isolated by a technique involving the ingestion of latex beads by the cells. Plasma membrane isolated from Sindbis virus-infected cells contained only one (E1) of the three (E1, E2, and C) structural proteins of this virus. When the latex beads were pretreated with either polylysine or DEAE-dextran, plasma membrane obtained from Sindbis virus-infected cells contained all three structural proteins and PE2, a precursor to one of the structural proteins. In pulse-chase radiolabeling experiments with Sindbis virus-infected cells, it was possible to follow the appearance of the precursor protein (PE2) i the plasma membrane and its eventual conversion to E2. The appearance of Sindbis virus membrane proteins PE2 and E1 in the purified plasma membrane was not affected by the drug tunicamycin, an inhibitor of glycosylation. These experiments imply the following: (i) Cleavage of the Sindbis virus precursor polypeptide PE2 to E2 is not a prerequisite for its transport to the cell plasma membrane; (ii) transport of virus membrane proteins to the cell surface does not depend on glycosylation; and (iii) although all Sindbis virus structural proteins are associated with the plasma membrane, a generally accepted pairing of PE2-E1 or E2-E1 in the plasma membrane either does not exist or, if it does exist, involves a very weak interaction. The procedures used in this study also resulted in the successful isolation of plasma membrane from vesicular stomatitis virus-infected cells containing the glycoprotein, the matrix protein, and the nucleocapsid protein, a result that suggests that these proteins are located on the media side of baby hamster kidney cells grown in monolayer.

Animals↗
PubMed1980

Comparison of carbonated bupivacaine and bupivacaine hydrochloride for extradural anaesthesia.

A double-blind comparison of carbonated bupivacaine and bupivacaine hydrochloride in extradural anaesthesia was performed in 40 patients. No significant differences in the onset times, sensory blockade, motor blockade and duration of anaesthesia were demonstrated. Carbonated bupivacaine does not appear to offer any advantage over the hydrochloride salt for extradural anaesthesia.

Adult↗