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Biomedical subjects

M Butler

Publications and source records attributed to M Butler.

At least 73 records · Page 4Linked to original sources
PubMed1984

Pharmacokinetics of the major metabolites of D-penicillamine in patients with rheumatoid arthritis.

The pharmacokinetic disposition of D-penicillamine and its major metabolites, penicillamine cysteine disulfide ( PSSC ) and penicillamine disulfide ( PSSP ) has been studied in eight patients with rheumatoid arthritis. Plasma concentrations of D-penicillamine, PSSP and PSSC displayed similar characteristics in terms of times to maximum concentrations and biphasic elimination from plasma. Initial t1/2 (alpha) phase ranged from 0.86 to 4.41 h for parent drug and 0.81 to 4.41 h for metabolites. Final t1/2 (beta phase) ranged from 3.4 to 9.45 h for D-penicillamine and 5.62 to 21.7 h for the metabolites. Total drug and metabolites detected in urine accounted for 12.0 to 48.7% of oral drug.

Adult↗
PubMed1983

A new model of osteoarthritis in rabbits. I. Development of knee joint pathology following lateral meniscectomy and section of the fibular collateral and sesamoid ligaments.

A partial lateral meniscectomy procedure has been developed for the induction of a predictable and reproducible degenerative joint disease in knees of rabbits. The procedure adopted involves section of the fibular collateral and sesamoid ligaments and removal of 4-5 mm of the anterior lateral meniscus. In most experiments the animals are killed and tissues obtained for histologic examination at 6 weeks. Section of the ligaments alone (with or without penetration of the joint space) did not result in significant pathologic change. Significant degeneration was observed in tibial and femoral cartilage when the meniscus as well as the ligaments were cut, but the most extensive lesions were seen when a piece of the anterolateral meniscus was actually removed. These lesions included fibrillation, ulceration and erosion, "clone" and osteophyte formation, loss of chondrocytes, and loss of safraninophilic staining in the articular cartilage. The incidence and distribution of lesions with time following surgery were also investigated. Lesions were observed as early as 1-2 weeks post-surgery and increased in number and severity up to 12 weeks. A global scoring system has been devised to permit statistical comparisons of lesion incidence and severity in different groups of rabbits. This scoring system has enabled us to test drug efficacy in the rabbit lateral meniscectomy model of osteoarthritis.

Acid Phosphatase↗
PubMed1983

A new model of osteoarthritis in rabbits. II. Evaluation of anti-osteoarthritic effects of selected antirheumatic drugs administered systemically.

A battery of drugs with antirheumatic properties was tested for effects on the progress of osteoarthritis induced by a lateral meniscectomy procedure in knee joint cartilage of rabbits. Oral administration of the potent glucocorticoids, paramethasone acetate or triamcinolone, resulted in dramatic inhibition of cartilage degeneration. Significant protection against development of osteoarthritic lesions was also observed in rabbits treated with pirprofen or CGS 5391B but not with 9 other nonsteroidal antiinflammatory drugs. A marked reduction in joint pathology was also observed in rabbits treated with tribenoside (a glucofuranoside derivative) and with tamoxifen (an anti-estrogen). Slightly protective effects of borderline significance were observed with orgotein (a superoxide dismutase), gold sodium thiomalate, and D-penicillamine. Chloroquine and calcitonin were without effect. Therapeutic effectiveness of drugs in this model of osteoarthritis cannot be explained on the basis of their antiinflammatory properties.

Animals↗
PubMed1983

A new model of osteoarthritis in rabbits. III. Evaluation of anti-osteoarthritic effects of selected drugs administered intraarticularly.

A battery of steroidal and nonsteroidal antirheumatic drugs and protease inhibitors were tested by intraarticular injection for effects on osteoarthritis of the knees of rabbits subjected to partial lateral meniscectomy and section of the sesamoid and collateral fibular ligaments. Among the standard drugs, only the glucocorticoid, triamcinolone hexacetonide, and the protease inhibitor, tranexamic acid, exhibited significant anti-osteoarthritic activity. An experimental drug, GPA 2163, also offered some protection against joint degeneration. The nonsteroidal antiinflammatory drugs had no effect on the development of osteoarthritis in the model.

Animal Diseases↗
PubMed1983

The role of phosphatidylserine decarboxylase in brain phospholipid metabolism.

In brain, phosphatidylethanolamine can be synthesized from free ethanolamine either by a pathway involving the formation of CDP-ethanolamine and its transfer to diglyceride, or by base-exchange of ethanolamine with existing phospholipids. Although de novo synthesis from serine has also been demonstrated, the metabolic pathway involved is not known. The enzyme phosphatidylserine decarboxylase appears to be involved in the synthesis of much of the phosphatidylethanolamine in liver, but the significance of this route in brain has been challenged. Our in vitro studies demonstrate the existence of phosphatidylserine decarboxylase activity in rat brain and characterize some of its properties. This enzyme is localized in the mitochondrial fraction, whereas the enzymes involved in base-exchange and the cytidine pathway are localized to microsomal membranes. Parallel in vivo studies showed that after the intracranial injection of L-[G-3H]serine, the specific activity of phosphatidylserine was greater in the microsomal fractions than in the mitochondrial fraction, whereas the opposite was true for phosphatidylethanolamine. When L-[U-14C]serine and [1-3H]ethanolamine were simultaneously injected, the 14C/3H ratio in mitochondrial phosphatidylethanolamine was 10 times that in microsomal phosphatidylethanolamine. The results demonstrate that serine is incorporated into the base moiety of phosphatidylethanolamine primarily through the decarboxylation of phosphatidylserine in brain mitochondria. A minimal value of 7% for the contribution of phosphatidylserine decarboxylase to whole-brain phosphatidylethanolamine synthesis can be estimated from the in vivo data.

Animals↗
PubMed1983

Lymphocyte subpopulations in primary immunodeficiency disorders.

Venous blood mononuclear cells from 42 children with primary immunodeficiency disorders and from controls matched for age were studied for lymphocyte subpopulations by E rosetting, surface immunoglobulin, and a panel of anti T cell monoclonal antibodies (OKT series). In 3 cases of severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency, very few circulating T or B cells were found. The other 7 cases of SCID all had normal or, in 3 cases, very high numbers of circulating B cells, but in 6 of these very few cells showed T cell markers. One child had very high numbers of B cells and T cells with an immature pattern of reactivity similar to that found on common thymocytes. In T cell deficient children no consistent pattern was found, but in those with cartilage hair hypoplasia with immunodeficiency there was a low helper (OKT4) to suppressor (OKT8) ratio and high numbers of circulating OKT10 positive cells. In cases of X-linked agammaglobulinaemia circulating B cells were not found but the pattern of T cell markers was normal. In cases of common variable hypogammaglobulinaemia there was a wide scatter of helper (OKT4) to suppressor (OKT8) cell ratios. Five children were studied before and after treatment with the synthetic thymic hormone preparation TP5. There were appreciable alterations in the pattern of staining with anti T cell monoclonal antibodies in 4 of these cases, but in 1 case only was this accompanied by improvements in clinical and immune function.

Agammaglobulinemia↗
PubMed1983

Transient thalamic hypodensity in lupus erythematosus with generalized seizures.

Computerized tomography revealed extensive bilateral hypodensity of the thalamus after an episode of severe arterial hypertension and convulsions in a patient with systemic lupus erythematosus. Radiologic and neurologic abnormalities were substantially resolved 1 week later. The unusual radiologic findings are discussed in relation to possible unique characteristics of vascular permeability in the thalamus.

Capillary Permeability↗
PubMed1983

High yields from microcarrier cultures by medium perfusion.

A culture perfusion system is described for the growth of anchorage-dependent cells on microcarriers. The critical component of this system is a column separator, which removes medium while allowing the microcarriers to remain in the culture. Amino acids and ammonia were analysed during cell growth of the perfusion culture. None of the amino acids was completely utilized. The accumulation of ammonia to 2.3 mM was observed and may be responsible for, or coincident with, events limiting further cell growth. It is suggested that oxygen deprivation and growth inhibitor accumulation, rather than nutrient depletion, are the major factors in limiting even higher cell yields.

Amino Acids↗
PubMed1982

Use of phospholipase A to compare phospholipid organization in synaptic membranes, myelin, and liposomes.

The pattern of fatty acid release from rat synaptic membranes in the presence of phospholipase A2 (Vipera russelli) was compared to that from liposomes comprised of phospholipids. Phospholipase A2 more readily attacked myelin and synaptic membranes than liposomes prepared from total phospholipids derived from myelin. Although hydrolysis of liposomal phospholipids occurred in the absence of added calcium, the presence of 2 mM CaCl2 or 2% bovine serum albumin significantly enhanced the phospholipase attack of liposomes, but not synaptic membranes of myelin. Phospholipase exhibited a marked preference for phospholipids containing docosahexaenoic acid (22:6) in the synaptic membranes, while with liposomes the pattern of released fatty acid reflected the fatty acid composition in the two-position of the phospholipids. Although either calcium or albumin markedly increased the phospholipase hydrolysis of liposomes, neither affected the hydrolysis of synaptic membranes or the pattern of fatty acid release from liposomes. It was concluded that the nonlipid constituents, particularly the proteins, of biomembranes were responsible for the organization of the phospholipids and accounted for the observed differences between liposomes and synaptic membranes with respect to enzymic accessibility.

Animals↗
PubMed1982

MDCK microcarrier cultured: seeding density effects and amino acid utilization.

The growth of Madin Darby canine kidney cells on microcarriers was studied at different cell seeding densities. Maximum growth was attained when a cell-to-bead ratio of 7:1 was used. Under these conditions an initial concentration of above 3 X 10(6) cells/ml resulted in a yield of over 2 X 10(6) cell/ml in 2 d. The amino acid utilization of cells from Dulbecco's modified Eagle medium was studied under the above conditions. Eight amino acids (arg, cys, gln, ile, leu, met, ser, and val) showed rapid and near complete depletion from the medium. Five amino acids (his, lys, phe, thr, and tyr) showed limited depletion. Two amino acids (ala and gly) were released into the medium by the cells.

Amino Acids↗
PubMed1982

A comparison of the virucidal properties of chlorine, chlorine dioxide, bromine chloride and iodine.

Chlorine dioxide, bromine chloride and iodine were compared with chlorine as virucidal agents. Under optimal conditions all disinfectants were effective at low concentrations, but each disinfectant responded differently to acidity and alkalinity. Disinfection by chlorine was impaired by the presence of ammonia, but the other disinfectants retained much of their potency. Disinfection of poliovirus by iodine resulted in structural changes in the virions as seen by electron micrroscopy, but the other disinfectants were able to inactivate poliovirus without causing any apparent structural changes.

Bromides↗
PubMed1982

Sidedness of phospholipid synthesis on brain membranes.

We have investigated the localization of the site of incorporation and the subsequent equilibration of newly synthesized phospholipids in brain membranes. Rats were injected intracranially with [3H]glycerol; the animals were killed at varying times afterwards, and microsomal fractions were isolated from the brains. In some cases, microsomes were subfractionated on sucrose gradients. Initially, most of the radioactive phosphatidylethanolamine appeared in a pool that reacted with the impermeable reagent trinitrobenzene sulfonic acid (TNBS). This probe presumably modified only the lipid on the outer face of microsomal vesicles (which may, in large part, consist of pinched-off endoplasmic reticulum). At 5 min after injection, the specific radioactivity of the TNBS-modified phosphatidylethanolamine (cytoplasmic face) was four times that of the unmodified (luminal or inner face) phosphatidylethanolamine. With time, the ratio of the specific activities in the modified and unmodified pools of phosphatidylethanolamine approached 1.0, with kinetics that suggested a half-time on the order of 30 min for in vivo conversion of the TNBS-accessible to the -inaccessible pool. This equilibration in specific activities could be the result of either translocation of phospholipids across endoplasmic reticulum membranes or conversion with time of initially labeled endoplasmic reticulum to other membranous organelles which form randomly oriented vesicles upon homogenization. A similar experimental design, using phospholipase C to hydrolyze outer face phospholipids preferentially, verified this conclusion for phosphatidylethanolamine and yielded similar results for phosphatidylcholine. Control studies measuring radioactive sucrose permeability indicated that neither TNBS nor phospholipase C treatment significantly disrupted microsomal vesicles under the conditions used.

Animals↗
PubMed1982

Isolation of indigenous enteroviruses from chemically treated and dewatered sludge samples.

Samples of wastewater sludge were examined for infectious enteroviruses before and after they had been chemically conditioned and dewatered. The least virus was recovered from the cake produced by filter pressing of sludge, which had a greatly increased solids content (39 to 45% [wt/vol]) relative to the untreated sludge (4.2 to 6.2% [wt/vol]) and in one plant was at pH 11 due to the lime conditioner used. Conditioning with a cationic polyelectrolyte before dewatering by centrifugation produced a watery sludge (2.7 to 5.3% [wt/vol]) from which high titers of infectious virus were recovered which were often greater than those isolated from the untreated sludge (0.6 to 1.4% [wt/vol]). This was thought to be due to saturation of virus and sludge floc adsorption sites by the polyelectrolyte, resulting in the liberation of virions from the sludge solids.

Calcium↗
PubMed1982

Quantitative and functional deficit of suppressor T cells in children with atopic eczema.

Helper (OKT4+) and suppressor (OKT8+) T cells were enumerated in 16 children with severe atopic eczema. Compared to controls (median 1 . 8) the ratio of OKT4+/OKT8+ cells in the patients was significantly higher (median 2 . 65, P less than 0 . 002). Functional suppressor activity in these patients was assessed by concanavalin A (Con A) activation and suppression of pokeweed mitogen (PWM) induced immunoglobulin production by plasma cells and Con A proliferation of T cells. In both assays a lack of suppression was shown (Con A/PWM, P less than 0 . 02; Con A/Con A, P less than 0 . 05). There was a significant inverse correlation between the helper/suppressor ratio and functional suppressor activity (P less than 0 . 01). These results indicate that a defect of T cell regulation does exist in atopic eczema and if it is of primary pathogenic importance, immunotherapy to restore the balance may prove useful.

Adolescent↗