PubMed Health⌕ Search

Biomedical subjects

F M Pope

Publications and source records attributed to F M Pope.

At least 127 records · Page 7Linked to original sources
PubMed1985

A highly polymorphic region 3' to the human type II collagen gene.

We have characterised a highly polymorphic region 1.3kb downstream of the human Type II collagen gene. It consists of a highly AT-rich tandem repetitive region (minisatellite) approximately 650bp long. Two alleles had been observed previously, differing in size by approximately 300bp. When this region was cloned from four unrelated individuals carrying the larger allele, DNA sequence data identified three alleles, suggesting far higher polymorphism than was originally supposed. This minisatellite was shown to be present in a single copy in the human genome, and to have arisen after the divergence of Old and New World monkeys.

Alleles↗
PubMed1985

Isolation of intermediate filament assemblies from human hair follicles.

We used developing human hair follicle cells for the isolation of hard alpha-keratin structural components. Intracellular dispersions examined by electron microscopy contained both individual alpha-keratin filaments and the tactoid-like filament assemblies observed in situ organized along subfibrillar arms of macrofibrils. The assemblies of average width 47 nm were composed of closely packed alpha-keratin filaments and originated from the initial filament arrays observed in sections of developing mammalian hair follicles. We have distinguished two types of assemblies: the para-like or hexagonally packed and the ortho-like spiral or whorl type. Axial banding extended across the width of filament assemblies, which suggested that hard alpha-keratin filaments pack in lateral register and form a lattice that contains interfilamentous bridges. We observed axial banding patterns with periods ranging from 20 to 22 nm, consistent with the 22-nm periodic structure deduced from x-ray diffraction studies and present in models proposed for hard alpha-keratin and other intermediate filaments. Preliminary biochemical studies of filaments and filament assemblies indicate that they consist of the closely related group of proteins (low-sulfur proteins) ubiquitous among extracts of hard mammalian keratins. Isolated hard alpha-keratin filament assemblies provide a new and valuable structural entity for investigating the assembly mechanisms involved in the formation of the filament-matrix framework found in hard mammalian keratin appendages.

Cytoskeleton↗
PubMed1985

Collagen genes and proteins in osteogenesis imperfecta.

Type I collagen is a heteropolymer of alpha 1(I) and alpha 2(I) chains, each of which is a separate product of genes localised to chromosomes 17 and 7 respectively. Molecular defects of type I collagen produce a group of inherited disorders of connective tissue primarily affecting bones, which are easily broken and collagen depleted (osteogenesis imperfecta). Sillence classifies these diseases into four groups, two of which are autosomal dominant and relatively mild, the others being either genetic lethals or responsible for very severe progressive disease. Here we describe two specific molecular abnormalities of type I collagen. One, a cysteine substitution in alpha 1(I) collagen, causes a mild Sillence type I disease, the other, a four base deletion in the C terminal extension of alpha 2(I) collagen, causes progressive Sillence type III disease in the homozygously affected patient and mild premature osteoporosis in his clinically symptomless parents. We have briefly reviewed a variety of other similar mutations causing various OI syndromes, which are tabulated, including various helical and non-helical deletions and a variety of structural protein changes. Several restriction fragment length polymorphisms for alpha 2(I) and alpha 1(II) collagens have also been described, and 5' EcoRI and 3' MspI polymorphisms for alpha 2(I) collagen segregate with Sillence type IV OI.

Base Sequence↗
PubMed1985

Abnormalities of the lungs and thoracic cage in the Ehlers-Danlos syndrome.

Twenty patients with the Ehlers-Danlos syndrome, (10 type I, six type II, and four type IV) were studied to assess the frequency of respiratory abnormalities in this condition. Five patients (25%) had had at least one episode of haemoptysis, but none had any defect of coagulation. There was a high frequency of recurrent sinusitis, notably in those with the type I syndrome. Two patients had bullous lung disease, one of whom (type IV) had had three pneumothoraces and subsequent pleurodesis; he also had tracheomegaly (the Mounier-Kuhn abnormality). Minor skeletal abnormalities such as pectus excavatum were common, particularly in patients with type IV disease. Three patients had the straight back syndrome. There were no consistent spirometric or lung volume abnormalities, but eight patients (40%) had a raised gas transfer coefficient (Kco), possibly due to an increased intrapulmonary vascular volume. Two other patients had very low values of Kco that were unexplained.

Adolescent↗
PubMed1985

Joint contractures and acroosteolysis in Ehlers-Danlos syndrome type IV.

Among a series of 10 patients with Ehlers-Danlos syndrome Type IV, several had peripheral joint contractures and 3 had acroosteolysis. The consequent deformities simulated the appearance of chronic inflammatory joint disease and hence, patients with this rare syndrome may come to the attention of rheumatologists. Recognition of Ehlers-Danlos syndrome Type IV is important because of the risk of early death from arterial rupture. The syndrome is also of theoretical importance as an "experiment of nature" illustrating functional consequences of deficiency of Type III collagen.

Adolescent↗
PubMed1984

Osteogenesis imperfecta: cloning of a pro-alpha 2(I) collagen gene with a frameshift mutation.

Osteogenesis imperfecta (OI), a brittle-bone disorder, constitutes a major group of the inherited diseases of connective tissue. We have been studying an autosomal recessive form of OI in which the severely affected patient has inherited two abnormal pro-alpha 2(I) collagen alleles from consanguinous parents. Previously, nuclease S1 mapping was employed to localize a defect in the mRNA coding for the pro-alpha 2(I) collagen carboxyl-propeptide. The mutation prevents incorporation of pro-alpha 2(I) chains into the normal type I procollagen heterotrimer resulting in secretion of only pro-alpha 1(I) homotrimers. Here we report complete characterization of the corresponding region of the altered gene. Polyacrylamide gel electrophoresis and Southern blot hybridization showed a small homozygous deletion in the pro-alpha 2(I) collagen gene of the patient and a heterozygous pattern in both parents. Genomic cloning of the patient's DNA revealed a four nucleotide frameshift deletion in exon 1 near the end of translation which apparently instigates use of a new termination codon four nucleotides 3' to the original site. The mutation identified in this OI patient directly demonstrates the critical role of the carboxyl-propeptides in chain selection and assembly during the biosynthesis of procollagen.

Amino Acid Sequence↗
PubMed1984

Retinoids increase the incorporation of D-[3H]galactose into epidermal glycoproteins.

All-trans retinoic acid increased the incorporation of D-[3H]galactose into particulate and soluble glycoproteins in the epidermis of cultured pig skin slices nearly two-fold. Increased incorporation of D-[3H]galactose was not blocked by tunicamycin. This effect was specific for D-[3H]galactose since the incorporation of D-[3H]glucosamine and L-[14C]leucine into epidermal glycoproteins was unaffected by all-trans retinoic acid. All-trans retinoic acid and 13-cis retinoic acid had quantitatively similar effects on D-[3H]galactose incorporation. All-trans retinyl acetate and an aromatic retinoic acid analogue ('Etretinate') were less effective. SDS polyacrylamide gel electrophoresis and fluorography showed increased incorporation of D-[3H]galactose into all epidermal glycoproteins in the presence of all-trans retinoic acid. There was no evidence for synthesis of new glycoproteins such as mucins.

Animals↗
PubMed1984

Lethal osteogenesis imperfecta congenita and a 300 base pair gene deletion for an alpha 1(I)-like collagen.

Broad boned lethal osteogenesis imperfecta is a severely crippling disease of unknown cause. By means of recombinant DNA technology a 300 base pair deletion in an alpha 1(I)-like collagen gene was detected in six patients and four complete parent-child groups including patients with this disease. One from each set of the patients' clinically unaffected parents also carried the deletion, implying that affected patients were genetic compounds. The study suggests that prenatal diagnosis should be possible with 100% accuracy in subjects without the deletion and with 50% accuracy in those who possess it (who would be either heterozygous--normal, or affected with the disease).

Base Composition↗
PubMed1984

Presence of translatable mRNA for pro alpha 2(I) chains in fibroblasts from a patient with osteogenesis imperfecta whose type I collagen does not contain alpha 2(I) chains.

RNA was extracted from the cultured fibroblasts from a patient with osteogenesis imperfecta previously shown to have type I collagen lacking alpha 2(I) chains. When the RNA was examined in a cell-free translation system from reticulocytes, the translation products included both pro alpha 1(I) and pro alpha 2(I) chains. When the poly(A)-enriched polysomal RNA was examined by blot hybridization with cDNAs for pro alpha 1(I) and pro alpha 2(I) chains, mRNAs for both pro alpha 1(I) and pro alpha 2(I) were seen. The ratio of mRNAs for pro alpha 1(I) to mRNAs for pro alpha 2(I) was about the same in the patient's fibroblasts as in control fibroblasts. The results suggested that the absence of pro alpha 2(I) chains in the type I pro-collagen from this patient is probably explained by a mutation which alters the structure of pro alpha 2(I) chains and thereby prevents incorporation of the pro alpha 2(I) chains into triple-helical procollagen.

Cell-Free System↗
PubMed1984

Nuclease S1 mapping of a homozygous mutation in the carboxyl-propeptide-coding region of the pro alpha 2(I) collagen gene in a patient with osteogenesis imperfecta.

The molecular defect in a patient with a moderately severe form of osteogenesis imperfecta was characterized by nuclease S1 mapping. Single-stranded 5' and 3' end-labeled DNA probes coding for 80% of the carboxyl-propeptide of the pro alpha 2(I) collagen gene were hybridized to mRNA isolated from cultured fibroblasts of the patient and his parents. Nuclease S1 digestion revealed a homozygous mutation in the patient and a heterozygous pattern in the consanguineous parents. As a result of the defect in the gene, none of the pro alpha 2(I) chains synthesized by the patient's fibroblasts were incorporated into a type I procollagen heterotrimer consisting of two pro alpha 1(I) chains and one pro alpha 2(I) chain. Cultured skin fibroblasts from the patient have previously been shown to secrete only pro alpha 1(I) trimers. As shown here, fibroblasts from both parents, who do not have osteogenesis imperfecta, secrete both pro alpha 1(I) trimers and normal type I procollagen. A further observation was that synthesis of pro alpha 2(I) chains was decreased in fibroblasts from the patient and his parents. The decrease in the synthesis of pro alpha 2(I) chains is not caused by decreased transcription of the pro alpha 2(I) collagen alleles, since the pro alpha 1(I)/pro alpha 2(I) mRNA ratios were normal in the patient and his parents.

Alleles↗
PubMed1984

Electrophoretic and immunoelectrophoretic analysis of pig epidermal plasma membrane glycoproteins.

he glycoprotein components of a plasma membrane-enriched fraction from pig epidermis were isolated by deoxycholate extraction and affinity chromatography on concanavalin A (ConA)-Sepharose 4B. Reduction with 5% 2-mercaptoethanol, electrophoresis on 10% polyacrylamide slab gels, and periodic acid-Schiff (PAS) staining resolved the major glycoproteins into at least 5 components of Mr 180K, 150K, 130K, 100K and 85K. Neuraminidase removed essentially all the sialic acid whether or not the glycoproteins were solubilized with detergents. Neuraminidase treatment increased the electrophoretic mobility of most components on one-dimension polyacrylamide gels, indicating their sialoglycoprotein nature. An antiserum was raised in rabbits against isolated epidermal plasma membrane glycoproteins. Isolated immunoglobulins were used in crossed immunoelectrophoretic analysis of the glycoproteins and produced 5 major immunoprecipitates. The glycoprotein nature of the immunoprecipitates was shown by their susceptibility to neuraminidase. Crossed immunoelectrophoresis was used to examine the lectin binding specificity of isolated epidermal plasma membrane glycoproteins. The immunoprecipitation patterns were affected strongly by Ricinus communis agglutinin (RCA), moderately by wheatgerm agglutinin (WGA), and weakly by soybean agglutinin (SBA). Peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), and Ulex europaeus agglutinin (UEA) had little effect on the immunoprecipitation patterns, indicating little interaction between epidermal plasma membrane glycoprotein and these lectins. Other glycoproteins and/or glycolipids must therefore be responsible for the binding of these lectins by epidermal cells.

Animals↗
PubMed1984

Ehlers-Danlos syndrome type IV mimicking non-accidental injury in a child.

This case report describes a child in whom non-accidental injury was initially suspected, but who was later shown to have autosomal dominant Ehlers-Danlos syndrome (EDS) type IV. Her mother and brother were also type III collagen deficient. This syndrome may be commoner than the small number of reported cases suggested and may sometimes explain previously undiagnosed easy bruising. The importance of recognizing this syndrome is stressed as it may save a great deal of embarrassment, frustration and anger for the family wrongly suspected of causing injury to their child.

Adult↗
PubMed1984

The clinical features of homozygous alpha 2(I) collagen deficient osteogenesis imperfecta.

The detailed clinical features and progress of a child with homozygous alpha 2(I) collagen deficiency are described. Clinically, the disease presents as severe progressive Sillence type III osteogenesis imperfecta. The main biochemical defect is the synthesis of an abnormal pro alpha 2(I) chain which does not associate with pro alpha 1(I) chains and therefore is not incorporated into triple helical trimers of type I procollagen which can be used to assemble collagen fibres.

Child, Preschool↗
PubMed1983

The molecular defect in a nonlethal variant of osteogenesis imperfecta. Synthesis of pro-alpha 2(I) chains which are not incorporated into trimers of type I procollagen.

Cultured fibroblasts were examined from a patient with a nonlethal form of osteogenesis imperfecta. As reported previously (Nicholls, A. C., Pope, F. M., and Schloon, H. (1979) Lancet 1, 1193), the cells synthesized and secreted a type I procollagen which lacked pro-alpha 2(I) chains and consisted of a trimer of pro-alpha 1(I) chains. No pro-alpha 2(I) chains were recovered from the medium under conditions in which nonhelical pro-alpha 1(I) and pro-alpha 2(I) chains were readily detected in the medium of normal fibroblasts incubated with the hydroxylase inhibitor, alpha, alpha'-dipyridyl. Examination of cellular proteins demonstrated that the fibroblasts synthesized both pro-alpha 1(I) and pro-alpha 2(I) chains. The cellular pro-alpha 2(I) chains did not, however, become disulfide-linked into dimers or trimers of pro-alpha chains. Since the association of pro-alpha chains during the biosynthesis of type I procollagen is directed by the conformation of the COOH-terminal propeptides, the data suggest that the pro-alpha 2(I) chains synthesized by the fibroblasts have a mutated structure in the COOH-terminal propeptides which markedly reduces their affinity for pro-alpha 1(I) chains. A further observation was that the ratio of newly synthesized pro-alpha (I):pro-alpha 2(I) chains in the patient's fibroblasts was 7.18 +/- 0.58 S.E. instead of the value of 2.25 +/- 0.16 S.E. seen in control fibroblasts. One possible explanation for the high ratio is that the proband is homozygous for a mutation altering the structure of the pro-alpha 2(I) chain and that a secondary effect of the structural mutation is a decreased rate of synthesis of pro-alpha 2(I) chains.

2,2'-Dipyridyl↗