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Biomedical subjects

G M Patterson

Publications and source records attributed to G M Patterson.

31 records · Page 2Linked to original sources

Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxa. II. Structures of laxaphycins A, B, D and E.

Laxaphycins A and B are the major components in an antifungal mixture of cyclic peptides from the terrestrial blue-green alga Anabaena laxa FK-1-2. NMR and MS spectral studies coupled with amino acid analysis indicate that the gross structures of laxaphycins A and B are cyclic (Aoc-Hse-E-Dhb-Hyp-Hse-Phe-Leu-Ile-Ile-Leu-Gly) where Aoc is a 3-aminooctanoic acid residue and cyclic (Ala-Hleu-Gln-N-MeIle-Hasn-Thr-Pro-Leu-Thr-Ade-Val- Hleu) where Ade is a 3-aminodecanoyl unit, respectively. Laxaphycin E, a minor cyclic undecapeptide, differs in gross structure from laxaphycin A in possessing a 3-aminodecanoic acid unit (Ade) in lieu of Aoc, whereas laxaphycin D, a minor cyclic dodecapeptide, differs from laxaphycin B in possessing a 3-aminooctanoyl unit (Aoc) instead of an Ade unit.

Amino Acid Sequence↗

Cytotoxic, antiviral indolocarbazoles from a blue-green alga belonging to the Nostocaceae.

6-Cyano-5-methoxy-12-methylindolo[2,3-alpha]carbazole and 6-cyano-5-methoxyindolo[2,3-alpha]carbazole are responsible for most of the cytotoxicity and antiviral activity associated with the blue-green alga Nostoc sphaericum EX-5-1. The compounds are active against HSV II and show weak cytotoxicity against KB and LoVo human carcinoma cell lines.

Antiviral Agents↗

AIDS-antiviral sulfolipids from cyanobacteria (blue-green algae).

A recently developed tetrazolium-based microculture assay was used to screen extracts of cultured cyanobacteria (blue-green algae) for inhibition of the cytopathic effects of the human immunodeficiency virus (HIV-1), which is implicated as a causative agent of AIDS. A number of extracts were found to be remarkably active against the AIDS virus. A new class of HIV-1-inhibitory compounds, the sulfonic acid-containing glycolipids, was discovered through the use of the microculture assay to guide the fractionation and purification process. The pure compounds were active against HIV-1 in cultured human lymphoblastoid CEM, MT-2, LDV-7, and C3-44 cell lines in the tetrazolium assay as well as in p24 viral protein and syncytium formation assays.

Antiviral Agents↗

Toxicity and partial structure of a hepatotoxic peptide produced by the cyanobacterium Nodularia spumigena Mertens emend. L575 from New Zealand.

A clonal isolate, termed L575, of the filamentous brackish-water cyanobacterium Nodularia spumigena Mertens emend. was found to produce a potent hepatotoxic peptide (50% lethal intraperitoneal dose for the mouse, 60 micrograms/kg) with chemical and toxicological properties similar to those of the hepatotoxic heptapeptides produced by other freshwater planktonic cyanobacteria. The isolate was made from a water sample collected in Lake Ellesmere, New Zealand, in 1980. The toxin, isolated and purified by high-performance liquid chromatography (HPLC) and analyzed by HPLC amino acid analysis, contained glutamic acid, beta-methyla-spartic acid, and arginine units in equivalent amounts. The fast-atom-bombardment mass spectrum of the toxin indicated the molecular weight to be 824. Batch cultures of strain L575 showed that the toxin content varied between 1.96 and 2.99 mg/g of cells and that a positive correlation between toxin content and chlorophyll a, but not biomass, was present.

Animals↗

Maternal immunization with P fimbriae for the prevention of neonatal pyelonephritis.

Rhesus monkeys (Macaca mulatta) were immunized with purified P fimbriae from Escherichia coli during the last trimester of pregnancy. Infants born of these mothers were compared with those from nonimmunized rhesus mothers. A delay in the onset of renal disease after bladder infection showed protection from passive immunization. This was associated with a high antibody titer in serum. In addition to delayed onset of renal infection, a decreased number of immunized monkeys developed pyelonephritis.

Animals↗

Cytotoxic, fungicidal nucleosides from blue green algae belonging to the Scytonemataceae.

Tubercidin, toyocamycin, and the corresponding 5'-alpha-D-glucopyranose derivatives of the nucleosides are frequently responsible for much of the cytotoxicity and antimycotic activity associated with extracts of cultured cyanophytes belonging to the family Scytonemataceae. The 5'-alpha-D-glucopyranoses of tubercidin and toyocamycin, for example, are the major cytotoxic and fungicidal nucleosides in Fijian Plectonema radiosum and Hawaiian Tolypothrix tenuis, respectively.

Antifungal Agents↗

Immunology of pyelonephritis. VIII. E. coli causes granulocytic aggregation and renal ischemia.

We studied renal venous blood after renal infection for its concentrations of leukocytes, complement and renin. In addition, we evaluated this blood for granulocytic aggregation and chemiluminescence of granulocytes. We found that very rapid activation of serum complement occurred with associated granulocytic aggregation and evident vascular occlusion and ischemia since renin rose rapidly. It appears that this early sequence of events will cause renal damage by ischemic change, as well as that known to occur from the inflammatory reaction.

Animals↗

Binding studies of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to the phorbol ester receptor in a mouse epidermal particulate fraction.

The preparation of [3H]lyngbyatoxin A by catalytic triton-proton exchange of lyngbyatoxin A and [3H]debromoaplysiatoxin by tritiation-debromination of aplysiatoxin is described. The dose-response curves for the binding of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to a mouse epidermal particulate fraction are virtually the same as the one previously described for [3H]12-O-tetradecanoylphorbol-13-acetate ([3H]TPA). The specific binding of [3H]TPA, [3H]-lyngbyatoxin A and [3H]debromoaplysiatoxin to the mouse epidermal particulate fraction is inhibited to the same degree by unlabeled TPA, teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin. This study indicates that TPA, lyngbyatoxin A and debromoaplysiatoxin bind to the same high affinity receptor in mouse skin.

Animals↗

Synthesis and in vitro activity of some methylenomycin analogs.

A cationic cyclopentannelation reaction has afforded a very simple route to a wide variety of methylenomycin analogs. The antibacterial activity of these readily accessible synthetic compounds parallels that of naturally occurring methylenomycin A. The in vitro antitumor activity of the synthetics assayed using human nasopharyngeal carcinoma (KB) cells is particularly promising.

Anti-Bacterial Agents↗

Regulation of scytophycin accumulation in cultures of Scytonema ocellatum. II. Nutrient requirements.

The effects of optimal sources and concentrations of major nutrients (supplying N, S, P, K+, Na+, Ca2+, Mg2+, and inorganic carbon) and organic buffers on growth and secondary metabolite accumulation in Scytonema ocellatum strain FF-66-3 were determined. Nitrate, phosphate, magnesium, and sulfur had no specific stimulatory or inhibitory effects on scytophycin accumulation within the range of concentrations that supported optimal growth. Calcium concentrations greater than those required for growth (0.1 mM) stimulated scytophycin accumulation. Sodium carbonate concentrations in excess of 0.25 mM strongly inhibited growth. Ammonium (2.5 mM) inhibited both growth and product formation. 3-[N-Morpholino]propanesulfonic acid at 3-5 mM effectively controlled pH and facilitated both growth and product formation.

Anti-Bacterial Agents↗

Tolytoxin and new scytophycins from three species of Scytonema.

Tolytoxin [1], the major cytotoxin associated with Scytonema mirabile strain BY-8-1, Scytonema burmanicum strain DO-4-1 and Scytonema ocellatum strains DD-8-1, FF-65-1, and FF-66-3, has been shown to be 6-hydroxy-7-O-methylscytophycin B. Minor amounts of three other new cytotoxic scytophycins, 6-hydroxyscytophycin B [2], 19-O-demethylscytophycin C [3], and 6-hydroxy-7-O-methylscytophycin E [4], have also been isolated from these cyanophytes. The gross structures and stereochemistry are based on nmr and cd analysis and on comparison with scytophycins A-E.

Antifungal Agents↗

The diagnosis of obliterative bronchiolitis after heart-lung and lung transplantation: low yield of transbronchial lung biopsy.

Obliterative bronchiolitis is the most significant long-term complication of lung and heart-lung transplantation characterized by the rapid development of obstructive airway disease. It is thought to be a manifestation of chronic rejection and has been treated, with limited success, with augmentation of immunosuppression. Early detection of obliterative bronchiolitis and prompt initiation of therapy may result in an improved outcome. The role of transbronchial biopsy has been reported in the diagnosis of acute rejection and infection but not for obliterative bronchiolitis. To study this problem we retrospectively reviewed the transbronchial biopsy results of patients with advanced clinical obliterative bronchiolitis, as defined physiologically. Between January 1, 1988, and December 31, 1991, 46 "sets" of adequate transbronchial biopsy specimens were obtained from 16 patients (15 heart-lung recipients and one double lung recipient). Seven sets of transbronchial biopsy specimens (15.2%) showed obliterative bronchiolitis by pathologic study. In four patients with severe clinical obliterative bronchiolitis, only one transbronchial biopsy specimen of seven (14.3%) showed obliterative bronchiolitis. The pathologic diagnosis of obliterative bronchiolitis was confirmed in three of these patients at the time of autopsy or retransplantation. Twelve patients were still alive at the end of the study period, and all experienced further deterioration of lung function typical for obliterative bronchiolitis. We conclude that the sensitivity of transbronchial biopsy for obliterative bronchiolitis is poor. Possible explanations for these results are explored.

Adolescent↗