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Biomedical subjects

B D Lake

Publications and source records attributed to B D Lake.

At least 73 records · Page 4Linked to original sources
PubMed1992

Mucolipidosis type IV. Presentation of a mild variant.

The authors report a 16-year-old girl with mucolipidosis type IV. She was referred because of deteriorating vision over the past three years. Corneal clouding with the appearance of cornea verticillata and retinal dystrophy were the main ophthalmological findings. Except for clumsiness no psychomotor retardation was present. Ultrastructural analysis of a conjunctival biopsy and cultured fibroblasts suggested a diagnosis of mucolipidosis type IV which was confirmed by biochemical studies. This patient represents the mildest described presentation of mucolipidosis type IV.

Adolescent↗
PubMed1991

Lysosomal storage of subunit c of mitochondrial ATP synthase in Batten's disease (ceroid-lipofuscinosis).

Immunochemical studies demonstrate that subunit c of mitochondrial ATP synthase is stored in the late-infantile, juvenile and adult forms of Batten's disease. It does not accumulate in the infantile form, or in other conditions involving lysosomal hypertrophy. These results suggest that the defective metabolism of subunit c is central to the pathogenesis of these three forms of Batten's disease.

Aged↗
PubMed1991

The role of histochemical investigations in metabolic disorders affecting the liver.

The application of histochemical techniques to the study of metabolic disorders affecting the liver can yield considerable information, provided the methods used are sound and the interpretation is not over-enthusiastic. The appropriate methods can give insight into liver function and can identify and localize a wide variety of carbohydrates, lipids, proteins and enzyme activities. It is often thought that tissue taken for histochemical analysis cannot be used for morphology, but properly prepared tissue will provide the architectural and cytological detail necessary for histological assessment. There are several advantages to the histochemical approach, the main ones being economy of use of the valuable tissue sample (in theory about 100 sections and tests can be done on a 1 mm depth of tissue) and that the results of the tests can be assessed in relation to the structure of the liver. There are two areas in which histochemical investigations are used: firstly, to detect cellular constituents, structures and cells not otherwise visible by routine methods. In this mode, histochemistry is an extension of the histological approach and constitutes a 'super haematoxylin and eosin' stain. Secondly, it is possible to assess enzyme activities and their localization, and in some well-defined instances to offer reliable indications of whether there is deficient activity, normal activity or enhanced activity. Although there is a body of opinion which believes that quantitative enzyme histochemistry is possible and reliable, the author has not found the data, in particular or lysosomal enzymes, to be reliable and remains unconvinced that this technique has a place in the study of pathological tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Histocytochemistry↗
PubMed1991

Recent biochemical and genetic advances in our understanding of Batten's disease (ceroid-lipofuscinosis).

Protein is the major component of the intra-lysosomal storage material which characteristically accumulates in Batten's disease. In the late-infantile, juvenile and adult forms of the disease, and in a form affecting sheep, this protein is principally composed of a single polypeptide, subunit c of mitochondrial ATP synthase. Subunit c is not stored in the infantile form of Batten's disease, supporting recent genetic data which suggest this is a distinct disease. Nor is subunit c found in storage material within other lysosomal storage diseases or in lipofuscin of old age. Subunit c storage, therefore, is specific for the later-onset forms of Batten's disease and indeed may be central to their aetiology.

Adult↗
PubMed1991

Infantile systemic hyalinosis: newly recognized disorder of collagen?

Four infants with stiff skin and painful joint contractures in the first few months of life are described. Other features included small papules, particularly on the face and trunk, perianal nodules, hyperpigmentation over the metacarpophalangeal joints and over the malleoli, gingival hyperplasia, persistent diarrhea, and failure to thrive. Two of these infants died before the age of 18 months. In each case hyaline material was found in the papillary dermis. Ultrastructurally, there was a distinctive fibrillogranular appearance in which a banding pattern could be observed. This material was also found within membrane-bound vacuoles in macrophages and fibroblasts. It had an appearance and localization identical with that of collagen type VI. These features are similar to those reported in juvenile hyaline fibromatosis. It is believed that these infants have a closely related, but nonetheless distinctive, inherited disorder of collagen.

Collagen Diseases↗
PubMed1990

Peripheral neuropathy in Leigh's disease.

Sural nerves were examined in 3 childhood cases of Leigh's disease (from 2 families), each with electrophysiological documentation of peripheral neuropathy. Postmortem confirmation of Leigh's disease was made in 2 cases; the third had characteristic CT scan appearances. Myelinated fibre densities were within normal limits, with no evidence of degeneration or regeneration. The myelin sheaths, however, appeared thin and this was confirmed quantitatively. In teased fibres there was no demyelination in 2 cases but some in 1 case. The findings suggest that there is hypomyelination of peripheral nerves leading eventually to demyelination.

Brain↗
PubMed1990

Depletion of alcohol (hexanol) dehydrogenase activity in the epidermis and jejunal mucosa in Sjögren-Larsson syndrome.

Using a histochemical technique, we have demonstrated a consistent deficiency of alcohol (hexanol) dehydrogenase activity within the epidermis and jejunal mucosa of patients with Sjögren-Larsson syndrome. Biochemical assay of the fatty alcohol: NAD oxidoreductase activity in cultured fibroblasts and leukocytes from these patients showed deficient activities compared with controls. The histochemical and biochemical results are complementary, and the simpler histochemical method can be used reliably for initial screening of patients with ichthyosis in whom a diagnosis of Sjögren-Larsson syndrome is suspected.

Alcohol Dehydrogenase↗
PubMed1989

Analysis of dolichyl pyrophosphoryl oligosaccharides in purified storage cytosomes from ovine ceroid-lipofuscinosis.

Ovine ceroid-lipofuscinosis is an inherited neurodegenerative disorder characterised by the accumulation of storage cytosomes in brain and visceral organs. Phosphorylated dolichol-containing compounds, largely in the form of dolichyl pyrophosphoryl oligosaccharides, have been shown to constitute 1-2% of the dry weight of storage cytosomes isolated from brain and pancreas, and 0.5 and 0.1% respectively of storage cytosomes isolated from liver and kidney. The carbohydrate portion of these glyconjugates in storage cytosomes isolated from brain, pancreas and liver consisted of a series of oligosaccharides of composition Man2-9GlcNAc2, with Man5-8GlcNAc2 predominating. The concentrations of dolichyl pyrophosphoryl oligosaccharides in storage cytosomes from ovine ceroid-lipofuscinosis are much higher than has been reported for endoplasmic reticulum, their normal functional location.

Animals↗
PubMed1989

Lysosomal storage of the DCCD reactive proteolipid subunit of mitochondrial ATP synthase in human and ovine ceroid lipofuscinoses.

The ceroid lipofuscinoses (Batten's disease) are a group of neuro-degenerative lysosomal storage diseases of children and animals that are recessively inherited. In the diseased individuals fluorescent storage bodies accumulate in a wide variety of cells, including neurons. The material stored in the cells of sheep affected with ceroid lipofuscinosis is two-thirds protein. The stored material does not arise from lipid peroxidation or a defect in lipid metabolism, and the lipid content is consistent with a lysosomal origin for the storage bodies. The major protein stains poorly with Coomassie blue dye and is soluble in organic solvents. It has an apparent molecular weight of 3,500 and its amino acids sequence is identical to that of the dicyclohexylcarbodiimide (DCCD) reactive proteolipid, subunit c, of mammalian mitochondrial ATP synthases. Apart from removal of mitochondrial import sequences, it has not been modified post-translationally. At least 50% of the mass of the storage bodies is composed of this protein. A minor protein sequence related to the 17-kDa subunit of vacuolar H(+)-ATPase is also found in storage bodies isolated from pancreas. As in humans and cattle, the ovine protein is the product of two expressed genes named P1 and P2. In normal and diseased animals there are no differences in sequences between P1 cDNAs or P2 cDNAs, nor do levels of mRNAs in liver for P1 or P2 differ substantially between normal and diseased animals. Both normal and diseased sheep also express a spliced pseudogene encoding amino acids 1 to 31 of the mitochondrial import presequence. The peptides they encode differ by one amino acid; arginine-23 is changed to glutamine in the diseased sheep. Storage bodies isolated from brains and pancreas of children affected with the juvenile and late infantile forms of ceroid lipofuscinosis also contain large amounts of material that is identical to subunit c of ATP synthase. However, the protein is not present in storage bodies isolated from brains of patients affected with the infantile form of the disease, and these storage bodies contain other unidentified proteins. It is possible that the cause of ovine, juvenile and late infantile ceroid lipofuscinoses is related to a defect in degradation of the subunit c of mitochondrial ATP synthase.

Amino Acid Sequence↗
PubMed1989

Glycoconjugates in storage cytosomes from ceroid-lipofuscinosis (Batten's disease) and in lipofuscin from old-age brain.

The ceroid-lipofuscinoses (CL) are a group of inherited diseases characterised by the accumulation, in brain, of autofluorescent storage cytosomes which have similar histochemical staining properties to lipofuscin, the neuronal wear and tear pigment of old-age brain. The storage cytosomes stain strongly with periodic acid-Schiff reagent (PAS), indicating the presence of carbohydrate. In brain from each childhood form of CL, concentrations of phosphorylated dolichol (Dol-P) are 10- to 20- fold higher than in age-matched controls. Brain Dol-P concentrations are also increased between 2 and 5- fold in several different lipidoses and in elderly subjects. Much of the Dol-P which accumulates is located within the storage cytosomes. Dol-P constitutes 2-3% of the dry weight of storage cytosomes from juvenile and late-infantile CL, and 0.3-0.7% of storage cytosomes from infantile CL, ovine CL and of lipofuscin isolated from old age brain. The bulk of the Dol-P in CL brain and in isolated storage cytosomes is present as dolichyl pyrophosphoryl oligosaccharides (Dol-PP-OS). The constitutions of the oligosaccharide moieties differ in the various forms of the disease. Histochemical analysis of frozen sections of unfixed brain after extraction by various lipid solvents indicates that the major part of the PAS positive intraneuronal material in CL brain and in old-age brain has the extraction properties of Dol-PP-OS. Carbohydrate represents 4-7% of the dry weight of CL storage cytosomes and of lipofuscin. The major monosaccharide components are mannose, N-acetyl glucosamine, glucose and galactose. Depending on the form of the disease studied, up to 40% of this material can be accounted for by Dol-PP-OS. Polyacrylamide gel electrophoresis of storage cytosomes followed by lectin blotting demonstrates several low molecular weight components which bind concanavalin A. These do not coelute with the major protein components and may well be Dol-PP-OS. We conclude that Dol-PP-OS are concentrated in storage cytosomes in CL and are one of their major glycoconjugate components.

Aging↗
PubMed1989

Prenatal diagnosis of infantile sialic acid storage disease in a twin pregnancy.

A diagnosis of infantile sialic acid storage disease was made in an infant who died aged 17 months. In the mother's next pregnancy no morphological or biochemical abnormality was found in chorionic villi, amniotic fluid, cultured amniotic fluid cells or fetal blood and a normal boy was born. In the subsequent pregnancy an ultrasound scan revealed a twin pregnancy. Chorionic villus samples were obtained from both twins and microscopic and biochemical analysis indicated one twin to be affected with sialic acid storage disease. Selective fetocide was performed. The unaffected twin proceeded to term.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1989

Use of enzyme histochemistry in the diagnosis of pancreatoblastoma.

The macroscopic, light microscopic and ultrastructural findings in a case of pancreatoblastoma in a neonate are presented. No evidence for exocrine or endocrine secretion could be found by histochemistry, immunocytochemistry or electron microscopy. However, enzyme histochemical techniques to localize activity of 'glucose-6-phosphatase', acid phosphatase, esterase and esteroprotease supported both a pancreatic origin for the tumour and a biphasic pattern of differentiation.

Acid Phosphatase↗
PubMed1989

Fetal ascites: an unusual presentation of Niemann-Pick disease type C.

Two infants were seen with severe ascites detected before birth, a previously unreported presentation of Niemann-Pick disease type C. In the second infant no diagnostic storage cells were present in bone marrow. Confirmatory investigations were prompted by experience of the first case.

Ascites↗
PubMed1988

The diverse neurological features of Niemann-Pick disease type C: a report of two cases.

Two cases of Niemann-Pick disease type C are described in order to illustrate the variable neurological features of this rare condition. One presented with a predominantly akinetic-rigid syndrome at the age of 5 years. The second developed progressive ataxia, accompanied by a vertical gaze palsy, when she was 13. Neither patient had hepatosplenomegaly; the diagnosis of Niemann-Pick disease type C was based on finding foamy storage cells in bone marrow aspirates.

Adolescent↗