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B D Lake

Publications and source records attributed to B D Lake.

At least 19 recordsLinked to original sources
PubMed1992

Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease).

The ceroid-lipofuscinoses (Batten disease) are neurodegenerative inherited lysosomal storage diseases of children and animals. A common finding is the occurrence of fluorescent storage bodies (lipopigment) in cells. These have been isolated from tissues of affected sheep. Direct protein sequencing established that the major component is identical to the dicyclohexylcarbodiimide (DCCD) reactive proteolipid, subunit c, of mitochondrial ATP synthase and that this protein accounts for at least 50% of the storage body mass. No other mitochondrial components are stored. Direct sequencing of storage bodies isolated from tissues of children with juvenile and late infantile ceroid-lipofuscinosis established that they also contain large amounts of complete and normal subunit c. It is also stored in the disease in cattle and dogs but is not present in storage bodies from the human infantile form. Subunit c is normally found as part of the mitochondrial ATP synthase complex and accounts for 2-4% of the inner mitochondrial membrane protein. Mitochondria from affected sheep contain normal amounts of this protein. The P1 and P2 genes that code for it are normal as are mRNA levels. Oxidative phosphorylation is also normal. These findings suggest that ovine ceroid-lipofuscinosis is caused by a specific failure in the degradation of subunit c after its normal inclusion into mitochondria, and its consequent abnormal accumulation in lysosomes. This implies a unique pathway for subunit c degradation. It is probable that the human late infantile and juvenile diseases and the disease in cattle and dogs involve lesions in the same pathway.

Amino Acid Sequence↗
PubMed1992

Stored dolichyl pyrophosphoryl oligosaccharides in Batten disease.

Each of the 3 childhood forms of Batten disease, juvenile (JB), late-infantile (LIB), and infantile (IB), have abnormally high brain concentrations of dolichyl pyrophosphoryl oligosaccharides (Dol-PP-OS). In this study, the carbohydrate portions of Dol-PP-OS were analysed: in JB and LIB, they range in size from Man2GlcNAc2 to Glc3Man9GlcNAc2, predominant components being Man5-7GlcNAc2 and Glc3Man7GlcNAc2. In IB, they range from Man6-9GlcNAc2, no glucose containing oligosaccharides being identified. In Batten disease, the main subcellular location of Dol-PP-OS is within storage material, where it represents up to 7% of the dry weight. [3H]-Mannose incorporation experiments with cultured fibroblasts show that synthesis of Dol-PP-OS in JB is normal. We infer that the glycosylation intermediate Glc3Man9GlcNAc2-PP-dolichol is synthesised normally within the endoplasmic reticulum in Batten disease, but that catabolic derivatives accumulate within the lysosomes. It is unclear whether this process is central to the pathogenesis of the disease, though in IB a defect in the release of mannose residues from Dol-PP-OS is a distinct possibility.

Carbohydrate Sequence↗
PubMed1992

Intraepidermal collagen type VII in dystrophic epidermolysis bullosa: report of five new cases.

The presence of intraepidermal collagen type VII has recently been used to define a subgroup of patients with mild dystrophic epidermolysis bullosa (DEB). This subgroup demonstrates virtual resolution of blistering during infancy despite often severe neonatal blistering. Using the antibody LH7.2, we have detected intraepidermal collagen type VII in five cases with DEB. These represent a much wider spectrum of clinical features and of intraepidermal and basement membrane zone (BMZ) staining patterns. Only one of our cases had features consistent with reported cases. Sequential skin biopsies from this case showed a marked change towards normal within 6 months of birth, paralleling the clinical improvement. The other four cases had sparse epidermal deposits of collagen type VII and included an affected foetus with autosomal recessive DEB. These findings suggest that the frequency of intraepidermal LH7.2 in DEB may be much higher than previously thought. The presence of abundant intraepidermal collagen type VII is of prognostic significance and can disappear over months. We recommend that biopsies of infants suspected of having EB are taken during the neonatal period.

Adolescent↗
PubMed1992

Restrictive dermopathy: a disorder of fibroblasts.

Restrictive dermopathy is a rare, lethal genodermatosis, characterized by a thin, tightly adherent skin which causes a dysmorphic facies, arthrogryposis and respiratory insufficiency. The recorded cases to date show a remarkable phenotypic similarity. Thinning of the dermis and the arrangement of collagen in parallel bundles appear to be constant findings. We have found many dead and degenerating fibroblasts in the dermis on ultrastructural examination, and have demonstrated their poor growth in vitro. Studies of collagen from a skin sample showed a marked increase in mature cross-links, indicating a decrease in skin collagen turnover. These findings suggest a primary disorder of fibroblasts, and may explain the apparent arrest in growth and differentiation of the skin which appears to be important in the pathogenesis of this rare condition.

Bone and Bones↗
PubMed1992

Intestinal pseudo-obstruction with deficient smooth muscle alpha-actin.

We describe a 48-year-old woman with chronic constipation since early childhood who has an intestinal myopathy associated with a hitherto undescribed absence by immunostaining of smooth muscle alpha-actin confined to the intestinal circular muscle. There were no abnormalities in other contractile proteins (myosin, tropomyosin, filamin, caldesmon or desmin) and despite the abnormality of a contractile protein isoform in the circular muscle, no significant morphological changes were identified by light microscopy or ultrastructural examination. A possible developmental mechanism for the observed change is proposed. The use of specific antibodies to isoforms of contractile proteins may have potential value in the study of intestinal myopathies.

Actins↗
PubMed1992

Clinical, histologic, and ultrastructural findings in two cases of infantile systemic hyalinosis.

Two unrelated infants had stiff skin and painful joint contractures in the first few months of life. Other features included gingival hyperplasia, small papules on the face and trunk, perianal nodules, and bloody diarrhea. Hyaline material was evident in the papillary dermis and gut mucosa in both patients. Ultrastructural examination revealed a distinctive fibrillogranular appearance. These infants have the same clinical, histologic, and ultrastructural features as four infants we reported previously with infantile systemic hyalinosis. One of the patients described here demonstrated some features that overlap with those of juvenile hyaline fibromatosis.

Biopsy↗
PubMed1992

Persistent gastrointestinal symptoms after correction of malrotation.

Persistent vomiting, diarrhoea, or intolerance of feeding, are well recognised problems in children after surgical correction of intestinal malrotation. Conversely, intestinal malrotation is a common accompaniment of chronic idiopathic intestinal pseudo-obstruction. We investigated motor activity of the small intestine during fasting in eight children who had persistent vomiting, intolerance of full enteral feeding, or severe diarrhoea after surgical correction of intestinal malrotation. Abnormality of motor function similar to that found in neuropathic pseudo-obstruction was found in seven of the eight patients. Persistence of symptoms after surgical correction of a malrotation is associated with a motility disturbance which seems to be due to a defect of intrinsic enteric innervation. Such a defect may be important in the aetiology of the malrotation.

Child, Preschool↗
PubMed1992

Gastric antral dysrhythmias in children with chronic idiopathic intestinal pseudoobstruction.

Chronic idiopathic intestinal pseudoobstruction is a serious disorder of intestinal neuromuscular function resulting in recurrent episodes of intestinal obstruction, and is caused by primary disease of the enteric nerves or enteric smooth muscle. Gastric electrical control activity detected by the non-invasive technique of surface electrogastrography was investigated in 11 children (0.1-16 years) with proven chronic idiopathic intestinal pseudoobstruction (four with known disease of the enteric nerves, three with disease of smooth muscle cells, and four without defined pathology), to determine whether abnormalities were present and whether these were useful in detecting the underlying pathology. Abnormalities were present in eight of 11 patients. Persistent tachygastria (electrical control activity frequency > 5 cycles/minute) was found in three patients, all with a proven neuropathy. A continuously irregular frequency was found in five patients, three with a proven myopathy and two with undefined pathology. A normal electrical control activity frequency was present in three patients, one with a proven neuropathy and two with undefined pathology. It is suggested that this non-invasive technique may provide a useful screening test of the pathophysiological basis of the functional obstruction in children with chronic idiopathic intestinal pseudoobstruction.

Adolescent↗
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↗
PubMed1979

Congenital fibre type disproportion myopathy. A histological diagnosis with an uncertain clinical outlook.

Nine children with congenital fibre type disproportion (CFTD) are described. Their muscle biopsies contained type 1 fibres which were smaller than the largest type 2 fibres by at least 13.5%. Attention is drawn to the variable natural history of this disorder which generally carries a good prognosis but may sometimes be associated with fatal respiratory problems. For important therapeutic, genetic, and prognostic reasons CFTD must be distinguished from other conditions with similar histochemical or clinical features.

Biopsy↗
PubMed1978

Disordered intestinal function in glycogen storage disease.

The classical features of Type I glycogen storage disease (McKusick 23220) (GSD) are hepatomegaly, hypoglycaemia, and acidosis, enlargement of the kidneys and short stature. Glucose-6-phosphatase (EC 3.1.3.9) activity is defective not only in liver and kidney but also in small intestine (Field et al., 1965). In addition to the classical features, many patients suffer from episodes of diarrhoea (Fine et al., 1969). At the Hospital for Sick Children, Great Ormond Street, patients with the commoner forms of hepatic glycogen storage disease have episodes of diarrhoea or loose stools more commonly than was suspected. We have investigated small intestinal function in three patients with Type I GSD by both in vitro and in vivo techniques.

Diarrhea↗
PubMed1978

Early-juvenile Batten's disease--a recognisable sub-group distinct from other forms of Batten's disease. Analysis of 5 patients.

In most cases where rectal biopsy is performed to diagnose Batten's disease, there is good correlation between biopsy appearance, age of onset, clinical course and electrophysiological parameters. As a result 3 forms of the disease have been recognised; infantile, late infantile and juvenile. In a review of rectal biopsy in Batten's disease at the Hospital for Sick Children, Great Ormond Street, we have studied the few cases in which no such correlation appeared to exist. In 5 the features are sufficiently similar to suggest a further recognisable sub-group which could be descriptively called "early juvenile". The clinical course, electrophysiological features and the absence of vacuolated lymphocytes in this subgroup are as found in the late infantile form, whereas the biopsy findings are identical to those of the juvenile form. By analogy with some of the mucopolysaccharidoses we speculate that the genes of the late infantile and juvenile forms of Batten's disease are allelic and that the "early juvenile" sub-group is a genetic compound presenting as an intermediate phenotype.

Child↗
PubMed1978

Hirschsprung's disease: an appraisal of histochemically demonstrated acetylcholinesterase activity in suction rectal biopsy specimens as an aid to diagnosis.

Suction rectal biopsy specimens, from a series of 168 infants and children with constipation and other gastrointestinal problems, were stained with a sensitive acetylcholinesterase method, and the results were compared with routine histology, radiology, anorectal manometry, and the final diagnosis. In all cases of Hirschsprung's disease, there was an increase in numbers and sizes of cholinergic nerves in the lamina propria and muscularis mucosae. No false-positive or false-negative results were found. The test was found to be more reliable and consistent than other methods available.

Acetylcholinesterase↗
PubMed1977

Adult Niemann-Pick disease: its relationship to the syndrome of the sea-blue histiocyte.

Three unrelated female patients with adult Niemann-Pick disease are described. All the patients had reduced coagulation factors and involvement of the marrow, liver, spleen and lungs. Two patients were shown to have abnormal platelet function; two patients also had pingueculas and a late onset of a menarche. Foam cells and sea-blue histiocytes were seen in the marrow and livers in all three patients, in the spleen in two patients in the lymph nodes in one patient. The clinical presentation, the histologic appearance, the histochemical staining reactions, the lipid analysis and the ultrastructure were all consistent with a diagnosis of adult Niemann-Pick disease. On the basis of these observations, it is clear that adult Niemann-Pick disease is a cause of the syndrome of the sea-blue histiocyte. The existence of the syndrome of the sea-blue histiocyte as a separate entity is also questioned.

Adolescent↗
PubMed1977

Adynamic bowel syndrome. Report of a case with disturbance of the cholinergic innervation.

A case of adynamic bowel syndrome is described. Full thickness biopsies of the large bowel showed the presence of ganglion cells, no acetylcholinesterase positive nerves in the lamina propria, submucosa or among the smooth muscle cells of the circular and longitudinal muscle coats, and absence of the argyrophil plexus. Electron microscopic examination showed replacement of the normal axon bundle by vacuolated tracts with small round bodies in one area--probably viral. Neuronal cytoplasm also showed similar vacuolation. It is suggested that the damage to the cholinergic innervation may be caused by a neurotoxic agent.

Axons↗