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Biomedical subjects

E J Miller

Publications and source records attributed to E J Miller.

At least 91 records · Page 5Linked to original sources
PubMed1988

Non-invasive investigation of liver disease in haemophilic patients.

Liver biopsy specimens previously taken from 16 haemophilic patients with chronic non-A, non-B hepatitis were reviewed. The degree of fibrosis correlated with serum procollagen III peptide (sPIIIP) concentrations, measured both at the time of biopsy and 4.25 years later. Two patients with extremely high sPIIIP concentrations had collateral veins on computed tomography, suggesting portal hypertension. Twenty eight of 47 patients (60%) had splenomegaly on computed tomography, and of 28 patients in whom intravenous contrast medium was used, seven (25%) had collateral oesophageal veins. Serum procollagen III peptide estimations and computed tomography, both non-invasive investigations, indicated that hepatic fibrosis and portal hypertension had developed in a proportion of haemophilic patients with non-A, non-B hepatitis. Infection with the human immunodeficiency virus (HIV) may modify the course of this presumably cytopathic virus infection of the liver.

Adolescent↗
PubMed1988

Surgical treatment of stress urinary incontinence: a comparison of the Kelly plication, Marshall-Marchetti-Krantz, and Pereyra procedures.

Six hundred eighty patients surgically treated for stress urinary incontinence were observed annually for up to ten years to compare the efficacy and complications of three types of repair procedures. Although Marshall-Marchetti-Krantz procedures yielded the most effective repair in the immediate postoperative period, Kelly plications were equally corrective more than three years after surgery (69 and 66%, respectively). Both were superior to the original Pereyra urethropexies at all times. Repeat operations were more likely to fail than primary repairs. The efficacy of the Pereyra procedure was increased with the use of permanent suture. Marshall-Marchetti-Krantz procedures were not affected by suture selection. Pereyra procedures had more complications, many related to intravesical suture. Success rates of all procedures declined steadily with lengthening periods of observation. We conclude that Kelly plications and Marshall-Marchetti-Krantz procedures have similar long-term efficacy and complication rates. The use of intra-operative cystoscopy and permanent suture with the Pereyra procedure might make it competitive.

Absorption↗
PubMed1987

A peptide secreted by human alveolar macrophages releases neutrophil granule contents.

A monoclonal antibody was developed against an 8,000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-gamma, tumor necrosis factor, or interleukin 1 alpha or 1 beta. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes.

Antibodies, Monoclonal↗
PubMed1987

Packaging and delivery of bone induction factors in a collagenous implant.

Extracts of demineralized rat bones which contained factors stimulating bone induction were reconstituted with highly purified human type I collagen to provide a suitable and easily manipulated delivery system for surgical implantation. When implanted subcutaneously in rats, the implants governed and delineated the dimensions of the resulting bony tissue. It is proposed that this implant system has clinical application in the filling of osseous defects within the scope of orthopaedic and oral and maxillofacial surgery. It is presented here as a potential improvement over conventional implant materials without osteoinductive properties.

Animals↗
PubMed1987

Reduced risk of non-A, non-B hepatitis after a first exposure to 'wet heated' factor VIII concentrate.

The risk of post-infusion non-A, non-B hepatitis (NANBH) in patients receiving a first exposure to unheated or conventionally 'dry heated' factor VIII concentrates approaches 100%, implying invariable contamination of these products. Amongst 18 patients who received a first treatment with a 'wet heated' commercial concentrate, five (28%) developed asymptomatic NANBH, suggesting a more efficient inactivation of NANB agent(s) by this process. 2/9 (22%) of the batches of concentrate used in the study were implicated in NANBH transmission. One of those two batches, responsible for NANBH in four patients, had been prepared from a plasma pool containing an unusually large proportion of donations with high alanine aminotransferase (ALT) levels. A resulting high level of viral contamination in this batch may have been sufficient to override the effects of the sterilization process. All patients remained anti-HIV seronegative at 17-28 months of follow-up.

Adolescent↗
PubMed1987

Premenstrual syndrome: beneficial effects of periodic, low-dose danazol.

Danazol (200 mg/day) or placebo was administered to patients with premenstrual syndrome from the onset of symptoms until the onset of menses, for two cycles each, in a prospective, double-blind, crossover design. Eleven of 14 patients improved on danazol. The symptom scores with danazol were significantly lower than those with placebo (P less than .035). No side effects were reported from the medication. We conclude that danazol, given periodically and in a relatively low dose, appears to have a beneficial effect in the treatment of premenstrual syndrome.

Adolescent↗
PubMed1986

Localization of type V collagen with monoclonal antibodies in developing dental and peridental tissues of the rat and hamster.

The distribution of collagen type V in developing dental and peridental tissues was investigated with the indirect immunofluorescence technique using unfixed, frozen sections of jaws from 1-2 day old neonatal rats and hamsters. Immunostaining for type V collagens was found both intracellularly and extracellularly in dental tissues of mesenchymal origin. In non-dental tissues, weak immunostaining was observed in the mesenchymally derived stroma surrounding the developing molar tooth germs but was more pronounced in larger cells, probably young osteoblasts in close vicinity to alveolar bone, and in some cells within developing salivary glands. Decalcification revealed a strong immunostaining in the extracellular bone matrices. In the dental tissues, the mesenchymally derived cells of the papilla exhibited an intracellular staining for type V collagen. In odontoblasts, increased immunostaining over that of other pulpal cells was observed just prior to or coinciding with the onset of predentin secretion and reactivity remained high in fully differentiated odontoblasts. A weak staining was observed in predentin but only after the onset of mineralization. As was the case for bone, after demineralization the dentin matrix stained intensely for type V collagen. The results demonstrate that type V collagen is actively synthesized by mesenchymal cells of developing hard tissues and that this type of collagen is an intrinsic component of hard connective tissue matrices. The data suggest that in developing tooth germs type V collagen is not involved in the differentiation process of either odontoblasts or ameloblasts.

Animals↗
PubMed1986

Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase.

Purified Pseudomonas aeruginosa elastase cleaved human type III and IV collagens with the formation of specific cleavage products. Furthermore, type I collagen appeared to be slowly cleaved by both P. aeruginosa elastase and alkaline protease. These cleavage fragments from type III and IV collagens were separated from the intact collagen chains by SDS polyacrylamide gradient gel electrophoresis run under reducing conditions, and they were detected by their characteristic Coomassie blue staining pattern. The results of these studies suggest that the pathogenesis of tissue invasion and hemorrhagic tissue necrosis observed in P. aeruginosa infections may be related to the degradation of these collagen types by bacterial extracellular proteases.

Collagen↗
PubMed1985

Synthesis of [pro alpha 1(IV)]3 collagen molecules by cultured embryo-derived parietal yolk sac cells.

Electron immunohistochemical studies demonstrate that cultured embryo-derived parietal yolk sac (ED-PYS) carcinoma cells synthesize type IV collagen. This material has been isolated and characterized. The collagen obtained after limited pepsin digestion from the medium in which the cells are grown is composed of homogeneous components with a molecular mass of approximately 95 000 daltons. When chromatographed on (carboxymethyl)cellulose under denaturing conditions, the chains elute as acidic components slightly before the human alpha 1(I) chain and coincident with the position of elution of the pepsin-derived human alpha 1(IV) chain. This analysis indicates the presence of a single type of collagen chain in the pepsin-derived ED-PYS synthesized material. In addition, the profile of cyanogen bromide (CNBr) cleavage products obtained from the pepsin-derived ED-PYS cell collagen chains is essentially identical with that derived from the human alpha 1(IV) chain. Isolation of the medium collagen in the absence of pepsin digestion reveals the presence of two high molecular weight components equivalent in size to procollagen alpha chains. However, both high molecular weight products yield CNBr cleavage products that correspond to those obtained from the pepsin-derived alpha 1(IV) chain. The ED-PYS cell-associated collagens obtained with or without the use of pepsin contain components that are essentially identical with those isolated from the culture-medium collagen. These data provide definitive evidence for the existence of type IV collagen molecules composed solely of alpha 1(IV) procollagen chains and further document the usefulness of ED-PYS cells for investigating the biosynthesis of basement membrane components.

Animals↗
PubMed1985

Isolation, characterization, and amino-terminal amino acid sequence analysis of human neutrophil elastase from normal donors.

Human neutrophil elastase from normal donors has been purified using an isolation procedure which included sequential sodium chloride extraction, Aprotinin-Sepharose affinity chromatography, CM-cellulose ion-exchange chromatography, and AcA44 gel filtration chromatography. The inclusion of this last purification step was crucial for separating inactive lower molecular weight species from the active forms of neutrophil elastase and resulted in a higher specific activity of the final preparation. Sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis of the reduced purified protein demonstrated three polypeptides of Mr 31,000, 28,000, and 27,500. Four polypeptides were resolved on acid gel electrophoresis; each of the four possessed amidolytic activity. Furthermore, peptide analysis of Staphylococcus aureus V8 protease digests indicated that these polypeptides are structurally related to each other and represent microheterogeneity of the purified protein. The apparent isoelectric points of these four forms as determined by two-dimensional electrophoresis range from 6.1 to 6.7. By utilizing microsequencing techniques, the first 40 residues of neutrophil elastase have been determined and compared with the reported sequence of elastase isolated from leukemic myeloid cells. In addition, a high degree of homology was found within the amino-terminal regions of neutrophil elastase and the serine proteinases porcine elastase, bovine chymotrypsin, human factor D, and the beta chain of plasmin.

Amino Acid Sequence↗
PubMed1985

The structure of fibril-forming collagens.

Although collagen molecules are designed primarily to serve as constituents of supporting aggregates in various tissues, they are present as a relatively large family of proteins that exhibit a wide diversity in structural and chemical features. Molecular diversity is, of course, specified primarily by the different genes for synthesis of the various collagen chains. However, intracellular post-translational modifications of the nascent chains as well as extracellular processing of newly assembled molecules contribute to, and considerably amplify, the diversity specified by the genome. Moreover, the nature of the aggregates derived from various molecular species of collagen reflects this diversity. In this fashion, a great deal of chemical and biological variation is created in otherwise highly similar molecules such as those classified here as belonging to group 1. It is anticipated that further developments regarding these and other molecular species of collagen will considerably refine our understanding of the spectrum of structure and function associated with this unique family of proteins.

Amino Acid Sequence↗
PubMed1985

Pericyte form and distribution in rat retinal and uveal capillaries.

Ultrastructural morphometric techniques were used to assess differences in endothelial cells and in pericyte structure and distribution in rat retinal and uveal capillaries. Retinal capillaries were significantly smaller than those in the three different uveal vascular beds, all of which were similar in size. Approximately 10% of the capillaries in the retina and choroid were formed by three endothelial cells, compared with 30% and 46% of capillaries sampled from ciliary processes and iris, respectively. The percentage of the capillary circumference covered by pericytes (46-58%) and the percentage of capillary sections with pericyte nuclei (12-16%) were similar in retina, iris, and ciliary processes. Corresponding data for the choriocapillaris indicated that pericyte coverage of these capillaries was approximately 50% of that observed in the other eye microcirculations. The number of pericyte processes per capillary varied markedly in the different vasculatures, with an average of three for capillaries in the retina and choriocapillaris and nine to eleven for capillaries in the iris and ciliary processes. These marked differences in capillary dimensions are consistent with the well-known capillary hemodynamic and functional differences of these tissues; however, the significance of the differences in pericyte shape, frequency and distribution in the different vasculatures of the eye is less clear.

Animals↗
PubMed1985

Interaction of DNA with connective tissue matrix proteins reveals preferential binding to type V collagen.

The interaction of DNA with type I to VI collagens and laminin was studied in vitro in systems in which the connective tissue components were immobilized, as well as when in solution. In studies on immobilized components, significant binding of DNA was observed only for type V collagen, and the binding of radiolabeled DNA to this component could be effectively inhibited in a concentration-dependent manner by the addition of unlabeled DNA. Similar results were observed in solution assays in which it was observed that DNA binding to type V collagen was dependent on the native triple-helical conformation of the collagen. The preferential binding of DNA to native type V collagen may be due to the relative basicity of type V collagen chains, as well as the unique spatial arrangement of amino acid side chains in the native molecules. The data are of potential clinical relevance in that binding of DNA to type V collagen may represent at least one component of the mechanism whereby DNA and its immune complexes are deposited in connective tissues in certain pathologic conditions.

Animals↗
PubMed1984

Evidence that the collagen in the culture medium of Chinese hamster lung cells contains components related at the primary structural level to the alpha1(V) collagen chain.

The collagenous protein synthesized by cultured Chinese hamster lung (CHL) cells and present in the culture medium has been isolated after limited pepsin digestion and differential salt precipitation. Molecular size analysis of this material indicates that the CHL cell medium collagen contains chains which exhibit an apparent molecular mass of approximately 85,000 Da. When chromatographed on CM-cellulose under denaturing conditions, the reduced and alkylated CHL cell medium collagen chains elute slightly after the human alpha1(I) chain but well before the pepsin-derived alpha1(V) chain, which is the constituent chain present in the CHL cell cellular matrix collagen. Analysis of the peptides derived by CNBr cleavage of the CHL medium collagen chains by chromatography on CM-cellulose reveals, however, that these chains contain peptides which correspond both in size and in chemical properties to those derived from the alpha1(V) collagen chain, but clearly lack two peptides (alpha1(V)-CB4 and alpha1(V)-CB5) which are normally present in pepsin-derived alpha1(V) chains. Furthermore, analysis of the CHL cell culture medium collagenous material obtained without pepsin digestion indicates the presence of collagenous chains that exhibit after reduction a molecular mass of approximately 160,000 Da, which is smaller than the proposed size of the pro alpha1(V) collagen chain. These results demonstrate that the collagenous protein present in the culture medium of CHL cells is directly related at the primary structural level to the alpha1(V) collagen chain, and it is postulated that this material represents the large fragment derived from a collagenase cleavage of the [pro alpha1(V)]3 molecules present in the cell layer. Furthermore, these results and previous reports indicate that the only identifiable genetic type of procollagen chain synthesized by this cloned cell line in culture corresponds to the pro alpha1(V) chain.

Amino Acid Sequence↗
PubMed1984

An unusual pattern of peptide-bound lysine metabolism in collagen from an infant with lethal perinatal osteogenesis imperfecta.

Collagens extracted from bones, cartilage, dermis, and dura mater of an infant with type II (lethal perinatal) osteogenesis imperfecta were evaluated with respect to chain composition and chemical characteristics of their constituent chains. The results indicated that the various types of collagen were present in the indicated tissues in proportions that approximated normal tissues. Nevertheless, the constituent chains of collagens extracted from dermis, i.e., alpha 1(I), alpha 2(I), alpha 1(III), alpha 1(V), and alpha 2(V), chromatographed on carboxymethyl cellulose as though they possessed substantially lower overall positive charge than the homologous chains of normal tissues. Amino acid analyses of the chains confirmed this observation and showed that the chains lacked five to seven residues of lysine (plus hydroxylysine). It was subsequently shown that the apparent deficiency in lysyl residues was due, at least in part, to the presence of unusually high levels of allysine , a cross-link precursor formed from peptide-bound lysine under the catalytic action of lysyl oxidase. These results, in conjunction with previous results obtained on collagens from type II osteogenesis imperfecta tissues, suggest that aberrant fibril formation in this syndrome allows increased lysyl oxidase activity.

Amino Acids↗