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Biomedical subjects

M Butler

Publications and source records attributed to M Butler.

At least 55 records · Page 3Linked to original sources
PubMed1987

Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2.

Ten monoclonal antibodies raised against Alzheimer's neurofibrillary tangles (ANTs) were characterized for reactivity with heat-stable microtubule fractions from bovine and human brain. Five of the antibodies showed very little reaction, but the other five reacted strongly with heat-stable microtubule associated proteins (MAPs). The proteins recognized by these antibodies have estimated molecular weights similar to those of known heat-stable MAPs, tau (52-68 kd) and MAP2 (200-250 kd). That the proteins are indeed tau and MAP2 is demonstrated by reaction of electroblotted proteins with antibodies raised in mouse and guinea pig against bovine brain tau and MAP2. One anti-ANT antibody reacts only with tau, two bind strongly to tau and weakly to MAP2, one recognizes both tau and MAP2 equally well, and one primarily stains MAP2. Extraction of ANT with 2% SDS does not remove tau or MAP2 epitopes from ANT, indicating that epitopes shared with heat-stable MAPs are integral components of ANT. The existence of tau epitopes in ANT is also demonstrated by immunoblotting of ANT-enriched fractions with anti-tau antibodies. Most of the material recognized by anti-tau antibodies in ANT-enriched fractions is present in large molecules excluded by 3% polyacrylamide gel upon electrophoresis. Anti-tau antibodies immunostain ANT in immunofluorescence and immunoperoxidase studies. The immunostaining can be blocked by absorption of anti-tau antibodies with purified tau proteins from bovine brain. Not all ANTs in any given tissue section or isolated Alzheimer perikarial preparations, however, are stained by anti-tau antibodies. These results are consistent with previous studies that have demonstrated heterogeneity of ANTs. Whether this heterogeneity is due to biochemical modification of MAPs or absence of MAPs in some ANTs is unknown. The significance of what appear to be shared epitopes recognized by monoclonal antibodies in tau and MAP2, and the implications this may have on the pathogenesis of ANT formation, requires further investigation.

Alzheimer Disease↗
PubMed1986

Microheterogeneity of microtubule-associated tau proteins is due to differences in phosphorylation.

We have studied the heterogeneity of the microtubule-associated tau proteins using tau-specific antibodies and two-dimensional electrophoresis. Both monoclonal and polyclonal antibodies to tau proteins recognize five bands in cow brain microtubule proteins run on sodium dodecyl sulfate (SDS)-polyacrylamide gels, with apparent molecular weights between 56,000 and 66,000. Immunoblots of cow brain microtubules separated on two-dimensional gels, using nonequilibrium pH gradient electrophoresis in the first dimension and SDS-gel electrophoresis in the second, reveal that greater than 30 isoforms of tau exist. The tau proteins vary in pI from 6.5 to 8.5, with the higher-molecular-weight forms being more acidic. The microheterogeneity of tau is not induced by cycling of microtubules, because two-dimensional immunoblots of tau from total brain are almost identical to those of tau from cycled tubules. Adult rat brain tau, which appears as three doublet bands on SDS gels, also exhibits considerable isoelectric heterogeneity, as does tau from 7-day-old rats, which appears as only one band on SDS gels. After dephosphorylation of cow brain tau with alkaline phosphatase, the highest-molecular-weight band disappears on SDS gels. On two-dimensional gels, the number of tau variants decreases by more than half after dephosphorylation, and the more basic species increase greatly in intensity. Preliminary experiments with tau labeled in vivo with 32PO4 also indicate that the more acidic tau proteins are the more highly phosphorylated forms. Thus, isoelectric heterogeneity of tau proteins exists at all ages and is due, at least in part to differences in the state of phosphorylation of tau isoforms.

Alkaline Phosphatase↗
PubMed1986

Immunoreactive calcitonin in amyloid fibrils of medullary carcinoma of the thyroid gland. An immunogold staining technique.

A lymph node containing metastatic medullary carcinoma of the thyroid gland was examined immunohistochemically for the presence of calcitonin by light and electron microscopy. Electron microscopy showed dense, selective labeling of the tumor-associated amyloid fibrils and labeling of the scanty intracytoplasmic neurosecretory granules. By light microscopy, a few tumor cells showed strong staining, whereas the amyloid fibrils showed equivocal staining.

Amyloid↗
PubMed1986

Presence of fibronectin in articular cartilage in two animal models of osteoarthritis.

Fibronectin content was determined in articular cartilage in a spontaneous dog model and in a meniscectomy rabbit model of osteoarthritis. Determination of the fibronectin content of urea extracts of articular cartilage by an enzyme linked immunosorbent assay (ELISA) disclosed that degenerated cartilage contained from 10- to 40-fold more fibronectin than normal cartilage. The finding that cartilage fibronectin content was increased in both animal models suggests that elevated cartilage fibronectin content is a general feature of the osteoarthritic process. Immunoperoxidase studies disclosed that fibronectin was distributed throughout the matrix in hyaluronidase treated normal and osteoarthritic cartilage from both animal models, but quantitative differences in fibronectin were not observed by these techniques.

Animals↗
PubMed1985

A comparison of bipolar and monopolar diathermy probes in experimental animals.

The effects of monopolar and bipolar diathermy were studied in laboratory animals. The power required to coagulate transected vessels in air was established and the effect of immersion in saline and water during electrocoagulation was investigated. Tissue heat conduction from each type of probe was measured and compared. Tissue damage was assessed by light microscopy of histochemically stained sections. The bipolar system operated at a lower power output (13 W) with less heat conduction, and was unaffected by the surrounding medium.

Animals↗
PubMed1985

Growth limitations in high density microcarrier cultures.

The growth of anchorage-dependent animal cells on microcarriers has enabled treatment of these cell lines as quasi-suspension cultures allowing the production of high cell densities. Analysis of the parameters affecting the final cell yield shows that if an optimal microcarrier/cell seeding ratio is provided, the surface area for cell growth is unlikely to be limiting. The culture medium could become limiting to cell growth by nutrient depletion or through the accumulation of growth inhibitors. In batch cultures of MDCK cells the analysis of amino acid utilization showed that some amino acids are nearly completely depleted from the medium during the growth period. Glutamine in particular was rapidly consumed reflecting its likely role as a major energy source. The use of a novel perfusion system for such cultures produces much higher cell densities. In 500 ml cultures perfused at 1 ml/min most of the amino acids maintained a steady concentration. The glutamine concentration was reduced not completely depleted. Under these conditions the ammonia concentration of the medium increased to a value of 2.3 mM when cell growth ceased. This level of ammonia accumulation occurred in both perfused and unperfused cultures. Investigations of the parameters affecting the growth of BHK cells in microcarrier cultures showed the rapid utilization of glutamine which was optimal at an initial concentration of 4 mM. Glucose showed rapid but not complete utilization in these experiments. The ammonia accumulation in the medium was shown to be directly related to the initial glutamine concentration and under optimal conditions rose to a level of 2.5 mM. This level of ammonia was shown to be growth inhibitory when added to cultures during inoculation. Growth experiments using culture medium diluted with isotonic salt solutions showed that the final cell yield was not directly related to the medium dilution in either perfused or unperfused cultures. This suggests that the accumulation of a growth inhibitor is responsible for growth limitation rather than nutrient depletion. The measurements of ammonia accumulation suggest that this could be the growth inhibitor which limits the final cell yield.

Amino Acids↗
PubMed1984

SAMP lyase and AMP deaminase activity in rat parenchymal and kupffer cells in hepatocarcinogenesis.

SAMP lyase and AMP deaminase were determined in parenchymal and kupffer cells of rats fed either basal or carcinogen-enriched diets. Results were calculated on a U/mg protein and U/cell basis. Data indicated that although deaminase increased 1 1/2 to 2-fold in parenchymal cells on a U/mg protein and U/cell basis from rats fed carcinogen-enriched diets there was a greater increase in U/mg protein. In contrast, little to no increase was seen in kupffer cells. SAMP lyase, however, depicted a smaller increase in parenchymal cells of carcinogen-enriched diet fed rats, but a 4- to 5-fold elevation in kupffer cells regardless of whether the data were expressed in U/mg protein or U/cell. These data indicate that increased activity of AMP deaminase may be a result of resistance to degradation in parenchymal cells, whereas SAMP lyase elevations in kupffer cells may reflect an increase in enzyme concentration.

AMP Deaminase↗
PubMed1984

Inactivation of human rotavirus, SA11 and other enteric viruses in effluent by disinfectants.

A preparation of infectious human rotavirus, isolated from faeces and resuspended in wastewater effluent, was shown to be inactivated by chlorine, chlorine dioxide, ozone and peracetic acid. Infectivity was assayed in MA 104 cells by the detection of cell-associated viral antigen by immunofluorescence. The inactivation curves were similar to those reported for other enteric viruses. Human rotavirus was at least as resistant as poliovirus, coxsackievirus, echovirus and f2 coliphage and was strikingly less sensitive to inactivation than the simian rotavirus, SA11. The latter was generally the most sensitive of the six tested viruses yet is often taken as being representative of the human rotaviruses.

Chlorine↗
PubMed1984

The detection of rotaviruses in products of wastewater treatment.

Rotaviruses present in products of wastewater treatment were assayed in MA104 cells by indirect immunofluorescence. Levels in settled sewage, activated sludge and effluent were greater than 10(3) per litre in March and April but virus was not detected during later months. This pattern correlated with the decline in laboratory reports of human rotavirus infection.

Enzyme-Linked Immunosorbent Assay↗
PubMed1984

Comparison of systemic and cerebrovascular effects of isoflurane and halothane.

This study was carried out to compare the cerebral and systemic circulatory effect of halothane and isoflurane. Six mongrel dogs were anesthetized with 1.3 minimal alveolar concentration (MAC) (1%) halothane and were compared with six mongrel dogs anesthetized with 1.3 MAC (1.5%) isoflurane. Likewise, 6 dogs anesthetized with 1.7 MAC (1.3%) halothane were compared with 6 dogs anesthetized with 1.7 MAC (2%) isoflurane. Blood flow (using the radioactive microsphere technique) and cardiovascular measurements were obtained 2 hours after the induction of anesthesia and were repeated 5 more times at hourly intervals. The heart rate was similar in all groups of dogs, except that it was significantly lower with 1.7 MAC halothane. The mean arterial pressure was statistically higher with isoflurane at both concentrations than with halothane. The cardiac index was similar in all groups, except with 1.7 MAC isoflurane, when it was higher. At the early measurements, total cerebral blood flow (CBF) was above "normal" levels in all groups. At 1.3 MAC, the total CBF tended to be lower with isoflurane, but did not reach statistically significant levels. Blood flow decreased over time in all groups. The cerebral vascular resistance (CVR) mirrored the changes in blood flow, showing no difference between agents at 1.7 MAC, but the CVR with isoflurane was significantly higher at 1.3 MAC than it was with halothane. Regional cerebral blood flow showed marked differences. Regional flow to the hemispheres and the cortical gray matter showed that isoflurane tended to produce lower blood flow, particularly at the 1.3 MAC concentration. The reverse was true in the posterior fossa structures, with the brain stem and cerebellum showing higher blood flows with isoflurane, particularly at 1.7 MAC. Isoflurane may have several advantages over halothane for neurosurgical procedures.

Animals↗
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↗