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Biomedical subjects

M Skinner

Publications and source records attributed to M Skinner.

At least 181 records · Page 10Linked to original sources
PubMed1984

Nephelometric measurement of human serum prealbumin and correlation with acute-phase proteins CRP and SAA: results in familial amyloid polyneuropathy.

Prealbumin, a negative acute-phase reactant, has a role as a clinical index of patient status after inflammation, trauma, or surgery that is gaining recognition. We developed a rate nephelometric assay that allows quantitation of prealbumin levels in a large number of samples to be performed quickly, efficiently, and reproducibly. The generation of data by this method is more rapid and precise than the alternative measurement techniques of radioimmunoassay, radial immunodiffusion, and electroimmunoassay. Nephelometric analysis of serum prealbumin in 33 patients with familial amyloidosis showed significantly depressed concentrations compared with levels in normal individuals and in patients with primary and secondary amyloidosis. Prealbumin levels were compared with corresponding amounts of the acute-phase proteins C-reactive protein and serum amyloid A in the three amyloid groups. Lowered prealbumin concentrations corresponded to elevated levels of C-reactive protein and serum amyloid A in the sera from patients with primary and secondary amyloidosis. In the group with familial amyloidosis, however, the lower than normal levels of prealbumin did not correspond to elevations in C-reactive protein and serum amyloid A. Our data suggest that depressed plasma prealbumin concentrations noted in individuals with familial amyloidosis are not simply reflections of a negative acute-phase response.

Amyloid↗
PubMed1984

Cloning of human prealbumin complementary DNA. Localization of the gene to chromosome 18 and detection of a variant prealbumin allele in a family with familial amyloid polyneuropathy.

Prealbumin, a 55,000 Mr protein, is a normal constituent of human serum. In patients with familial amyloid polyneuropathy (FAP), an autosomal dominant disease, variant prealbumin molecules are found in association with systemic amyloid deposits. One variant prealbumin has a methionine for valine substitution at amino acid 30 and has been implicated in the pathogenesis of type 1 FAP. A prealbumin-specific complementary DNA clone has been isolated from an adult human liver library and used in Southern blot hybridization experiments to identify a unique NsiI restriction endonuclease site in the variant allele carried by type 1 FAP patients with the methionine for valine substitution. The complementary DNA clone has been used to analyse a panel of human-mouse and human--hamster somatic cell hybrid DNAs and localize the prealbumin gene to chromosome 18.

Alleles↗
PubMed1984

Colchicine in acute inflammation: stimulation of production of interleukin-1 and modulation of the acute phase serum amyloid A protein response.

The effects of colchicine on the acute phase serum amyloid A (SAA) response were studied in CBA/J mice to determine whether these effects are mediated via inhibition of interleukin-1 (IL-1) production. Prolonged pretreatment (72 h) with colchicine blunted the SAA response to stimulation with silver nitrate (AgNO3), while brief pretreatment (12 h) unexpected augmented SAA production. In a macrophage model, colchicine stimulated baseline production of IL-1 (SAA inducer and lymphocyte activating factor activities) and augmented lipopolysaccharide (LPS) induced IL-1 production. This indicates that colchicine does not inhibit amyloidosis via direct effects on early inducers of the acute phase SAA response.

Amyloid↗
PubMed1983

Different regulatory mechanisms for serum amyloid A and serum amyloid P synthesis by cultured mouse hepatocytes.

Regulation of the in vitro synthesis of the serum amyloid proteins A and P has been studied with hepatocyte cultures from CBA/J and C3H/HeJ mice. Liver cells were isolated by the collagenase perfusion technique and established for 48 h in the presence of fetal calf serum. Viable cells could then be maintained in the absence of serum for at least 72 h and in the presence of serum for up to 2 weeks. Serum amyloid A synthesis differed from serum amyloid P synthesis in three significant ways. 1) Serum amyloid A production was stimulated in the presence of fetal calf serum, whereas serum amyloid P was not; 2) serum amyloid A synthesis was increased 200% by monokine-rich macrophage supernatants while serum amyloid P was increased only 10 to 20%; 3) serum amyloid A synthesis was strikingly resistant to cycloheximide inhibition as compared with serum amyloid P and other liver proteins. It is concluded that the in vivo asynchrony of the acute phase serum amyloid A and serum amyloid P responses results at least in part from differences in regulatory mechanisms for their synthesis by hepatocytes.

Amyloid↗
PubMed1983

Bleeding manifestations in 100 patients with amyloidosis.

Focal or generalized hemorrhage is a commonly encountered clinical problem in patients with amyloidosis. In 100 patients with amyloidosis, 41 patients experienced one or more bleeding episodes: petechiae and ecchymoses (23), gastrointestinal tract bleeding (18), bleeding after a diagnostic procedure (eight), hematuria (three), hemoptysis (two), and miscellaneous (four). Severe hemorrhage was the cause of death in three patients. Bleeding occurred frequently in the absence of abnormalities of clotting tests, suggesting that hemorrhage in amyloidosis is most often due to amyloid infiltration of blood vessels. In this group of patients, an isolated factor X deficiency was not observed.

Amyloidosis↗
PubMed1983

The analysis of an anti-fluorescein cytotoxic response.

The detailed kinetics of the appearance of clones of anti-fluorescein cytotoxic T lymphocytes (CTL) in a primary limiting dilution response have been examined. The addition of factors from the supernatants of concanavalin A-stimulated rat spleen cell cultures was necessary to obtain linear dose-response curves and strong primary responses. In a standard primary response the maximum detectable number of specific clones was found, on day 5, to be derived from precursors having a frequency of 1 in 10 000 spleen cells. When limiting dilution cultures were restimulated on day 3, responses on day 5 were unaffected but new clones appeared on day 7 with a frequency of 1 in 1000. The emergence of the day-7 response depends on the addition of factor(s) on day 3. It is proposed that the early low frequency precursors detected on day 5 and the high frequency precursors detected on days 7-9 are derived from two stages in the differentiation lineage of CTL precursors. Restimulation of limiting dilution cultures involves not only the continued clonal expansion of primary responses but also the emergence of new "clones" of specific CTL.

Animals↗
PubMed1983

The enhancement of cultured spontaneous cytotoxic T cells from normal and athymic (nu/nu) mice.

Subsets of natural killer cells may be characterised by the target cell profile, cell surface markers and the effect of growth factors on the production of effector cells. The subset which appears in primary cultures (spontaneous or natural T killer cells) is enhanced by the supernatants of Con A-stimulated rat spleen cultures. The enhancement can be attributed to an increased number of clones rather than an expansion of clone size in 5-day cultures. With semi-purified IL-2 preparations, clones of spontaneous cytotoxic cells are also detectable in nu/nu spleen cultures. These results suggest such spontaneous cytotoxicity is a general phenomenon within cytotoxic responses.

Animals↗
PubMed1983

Biological markers in human lung carcinoma: an immunopathological study of six antigens.

Immunohistological methods were used to investigate the presence of calcitonin, thyrotrophin, carcinoembryonic antigen, beta pregnancy specific glycoprotein, human placental lactogen, and the beta subunit of human chorionic gonadotrophin in formalin fixed lung tumour tissue sections. Carcinoembryonic antigen was observed in 71% of 101 tumours studied (70%), beta 1 pregnancy specific glycoprotein in 66 of 97 tumours (68%), beta subunit of human chorionic gonadotrophin in 35 of 97 (36%), human placental lactogen in 19 of 97 (20%), calcitonin in 10 of 71 (14%), and thyrotrophin in one of 27 lung tumours studied. There appeared to be no direct association between the presence of any given marker and the presence of any other. Similarly, the association between the presence of a tumour marker and histological type was poor. This study shows that the presence of tumour markers is relatively common in human lung tumours.

Adenocarcinoma↗
PubMed1983

Use of abdominal fat tissue aspirate in the diagnosis of systemic amyloidosis.

The needle aspirate of abdominal fat was investigated for its sensitivity in giving a tissue diagnosis in 32 consecutive patients with systemic amyloidosis. The fat tissue aspirate was stained with Congo red and examined with a polarizing microscope. Positive results were obtained in 95% (18/19) of patients with primary (AL) amyloidosis, 66% (4/6) of patients with secondary (AA) amyloidosis, and 86% (6/7) of patients with the heredofamilial (AF) form. The overall positive yield was 88% (28/32). Abdominal fat tissue aspiration is proposed as a simple, rapid, and effective technique for the diagnosis of amyloidosis. The prevalence of positive results in known amyloid disease are comparable with the rectal biopsy specimen and are more frequent than gingival or skin biopsy specimens.

Abdomen↗
PubMed1983

Coronavirus mRNA synthesis involves fusion of non-contiguous sequences.

Positive-stranded genomic RNA of coronavirus MHV and its six subgenomic mRNAs are synthesized in the cytoplasm of the host cell. The mRNAs are composed of leader and body sequences which are non-contiguous on the genome and are fused together in the cytoplasm by a mechanism which appears to involve an unusual and specific 'polymerase jumping' event.

Base Sequence↗
PubMed1983

Nephelometric measurement of human serum amyloid P component (SAP).

Serum amyloid P component (SAP) is a normal constituent of human serum. A rate nephelometric technique has been developed that can measure this protein more rapidly and reproducibly than previously described methods. Materials required are simple and commercially available. Studies on 30 patients with amyloidosis show no difference in SAP levels from control patients. Rate nephelometry is a simple technique that could expand the ability to measure SAP beyond the research setting.

Amyloid↗
PubMed1982

The association of amyloid P-component (AP) with the amyloid fibril: an updated method for amyloid fibril protein isolation.

An amyloid fibril isolation procedure is proposed which uses citrate as well as saline washes to dissociate the calcium dependent linkage of amyloid P-component (AP) from the amyloid fibril. In two amyloid rich tissues, the amount of AP was quantitated in each saline and citrate wash and totalled 13.8% and 20.8% of the amyloid fibrils isolated. The amount of AP removed from these and 22 additional amyloid rich tissues was greater than had previously been recognized. AP protein was present in tissue only when amyloid fibrils were present. It could not be found in normal non-amyloidotic tissue, nor could it be found in tissue sediment after the fibrils were removed.

Amyloid↗
PubMed1982

The role of interleukin 1 in acute phase serum amyloid A (SAA) and serum amyloid P (SAP) biosynthesis.

The acute phase SAA and SAP profiles have been compared for localized and endotoxin induced inflammation in LPS responder and nonresponder strains of mice. The SAP profile can reflect a delay with respect to the start of the increase. Its maximum is on the order of ten times the nonacute phase concentration and elevated concentrations are sustained 24 to 48 hours after SAA concentration is rapidly decreasing to normal. The role of Interleukin 1, known to have an essential role in SAA production, was investigated for SAP production. Purified mouse IL 1 and rabbit IL 1 produced a minimal elevation of SAP concentration above normal values, especially when compared with their effects on SAA concentration. BCG infection was shown to synergistically augment SAA induction by LPS and was shown to enhance IL 1 production by macrophages in response to LPS. Unlike SAA synthesis, BCG-preinfection fails to synergistically augment the LPS-induced SAP response. BCG infection alone produced highly elevated and sustained increases in SAP concentration, whereas, the effect on SAA concentration was minimal. Macrophages appear to play an important role in SAP acute phase elevation, but the mechanism in different from that of SAA elevation.

Acute Disease↗