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Biomedical subjects

B W Little

Publications and source records attributed to B W Little.

At least 19 recordsLinked to original sources
PubMed2001

Extensive subdural mass.

An unusual case of a 62-year-old man with focal seizures, tinnitus, and progressive left hemiparesis due to an extensive subdural plasma cell granuloma is presented. Five-year clinical and radiologic follow-up demonstrating the chronic yet progressive nature of this granuloma is presented. This is the first report of focal calcification seen in an intracranial plasma cell granuloma. The imaging, neuropathologic, and clinical characteristics of this rare lesion are reviewed.

Brain Diseases↗
PubMed1993

Immobilized pH gradient focusing of alkaline proteins: analysis of the isoform composition of purified human non-secretory ribonucleases from kidney, liver and spleen.

Previous studies on the isoform composition of human ribonucleases (RNAases) have resulted in confusing and inconsistent results, presumably due to methodological problems in electrofocusing of alkaline proteins. In the present study, immobilized pH gradient (IPG) carrier ampholyte (CA) isoelectric focusing (IEF) and conventional CA-IEF have been evaluated for the analysis of the isoforms of human non-secretory RNAases purified from kidney, liver and spleen. CA-IEF proved unsuitable since the alkaline RNAase isoforms migrated into the cathode. IPG-CA-IEF, however, resolved the RNAase isoforms and marker proteins in the basic region of the gel matrix. The three RNAases had comparable isoform profiles, each with two protein bands with approximate pI values of 10.3 and 10.4. Western blotting showed that the two protein bands of each RNAase were immunoreactive (with polyclonal antibodies that recognize RNAase), indicating that the protein bands are RNAase isoforms. The present results provide reliable pI data on human RNAase isoforms and suggest that IPG-CA-IEF should be a suitable technique for analysing the isoforms of other alkaline proteins.

Blotting, Western↗
PubMed1993

Human non-secretory ribonucleases. I. Purification, peptide mapping and lectin blotting analysis of the kidney, liver and spleen enzymes.

Human non-secretory neutral ribonucleases (RNases) from kidney, liver and spleen have been purified and characterized. SDS-PAGE indicates that all three RNases are highly purified and have apparent mol. wts of 17-18 kDa. Kinetic analysis indicates that all three RNases have a broad pH optimum centred around 6.5, and all three have similar substrate specificities with significant preference for RNA and poly(U) when compared to poly(C), poly(A) and poly(G). All of the above data, as well as immunoblotting data using three polyclonal antibodies (anti-human liver RNase, anti-human pancreatic RNase, anti-human eosinophil-derived neurotoxin), indicate that the three proteins are highly purified and are non-secretory RNases (IIN). Further characterization by cyanogen bromide peptide mapping and extensive lectin blotting indicated no significant differences between the three human RNases. All three RNases appear to have very similar, if not identical, protein backbones and all three are glycoproteins which are recognized by lectins with specificity for GlcNAc, Fuc and, to a lesser extent, with specificity for Gal beta(1-4)GlcNAc. No significant tissue-specific differences were found among the three human non-secretory RNases.

Blotting, Western↗
PubMed1993

Human non-secretory ribonucleases. II. Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry.

The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase.

Base Sequence↗
PubMed1993

A new (two-repeat) octapeptide coding insert mutation in Creutzfeldt-Jakob disease.

We report a family in which the proband died of clinically typical, neuropathologically verified Creutzfeldt-Jakob disease; her still-living mother suffers from a progressive dementia of many years' duration, and her maternal grandfather died after a similar illness. The proband, her mother, and two of three young first-degree relatives all have an identical insert mutation in the PRNP gene consisting of a twice-repeated 24-nucleotide sequence in the region between codons 51 and 91.

Aged↗
PubMed1992

Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene.

An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.

Adult↗
PubMed1990

Large vascular plexiform neurofibroma of scalp: excision and coverage with free tissue transfer.

Diffuse neurofibroma (paraneurofibroma) is an unusual variant of neurofibroma in which the tumor cells diffusely infiltrate beyond the usual well-circumscribed boundary. Histological features of the tumor include both typical and plexiform neurofibroma. Although benign, diffuse vascularity with the possibility of life-threatening hemorrhage dictates treatment. The combination of preoperative angiography, wide surgical excision, and resurfacing the defect with well-vascularized tissue offers one-stage reconstruction and possible cure.

Adult↗
PubMed1988

Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).

We report a large French-Canadian kindred with 33 affected members in six generations showing early-onset autosomal dominant limb-girdle myopathy and contractures. This myopathy is unique because of its benign course, with many members only minimally impaired even in old age. Examination of affected members revealed mild to moderate proximal weakness and wasting. Contractures were observed at the elbows and ankles in all, while in some they were more widespread. Serum CK was either normal or slightly raised, and electrodiagnostic studies suggested a primary myopathy. Muscle biopsy revealed nonspecific features of a myopathy without fiber necrosis or regeneration. Cardiac involvement was absent clinically in all patients and at autopsy in two affected individuals. The similarities between four previously reported families and our own establishes this myopathy as a distinct clinicogenetic entity, for which we propose the name "Bethlem myopathy."

Adolescent↗
PubMed1988

Recurrent intracranial hemorrhage in an adult with moyamoya disease: case report, radiographic studies and pathology.

Moyamoya disease is an unusual vascular disorder highlighted by progressive bilateral internal carotid artery occlusion and collateralization of intracranial blood flow. Recurrent multifocal cerebral ischemic events and isolated intracerebral hemorrhage are known to occur in this disorder. We report a 52 year old man who over a nine year period had four apparent intracranial hemorrhages. Serial angiograms demonstrated the evolution of moyamoya disease. Pathologic examination confirmed multiple vascular lesions, including two that were clinically silent.

Adult↗
PubMed1987

Childhood giant axonal neuropathy. Case report and review of the literature.

Giant axonal neuropathy (GAN) is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. Typically seen are distal axonal swellings filled with 8-10 nm in diameter neurofilaments in central and peripheral axons, and intermediate filament collections in several other cell types. Many neurotoxins produce a morphologically similar neuropathy in humans and experimental animals. Defective nerve fiber energy metabolism has been postulated as a cause in these toxic neuropathies. It is possible that GAN represents an inborn error of metabolism of enzyme-linked sulfhydryl containing proteins, resulting in impaired production of energy necessary for the normal organization of intermediate filaments.

Axons↗
PubMed1987

Lyme disease: cause of a treatable peripheral neuropathy.

Peripheral nerve dysfunction was demonstrated in 36% of patients with late Lyme disease. Of 36 patients evaluated, 14 had prominent limb paresthesias. Thirteen of these had neurophysiologic evidence of peripheral neuropathy; neurologic examinations were normal in most. Repeat testing following treatment documented rapid improvement in 11 of 12. We conclude that this neuropathy, which is quite different from the infrequent peripheral nerve syndromes previously described in this illness, is commonly present in late Lyme disease. This neuropathy presents with intermittent paresthesias without significant deficits on clinical examination and is reversible with appropriate antibiotic treatment. Neurophysiologic testing provides a useful diagnostic tool and an important measure of response to treatment.

Adult↗
PubMed1986

Familial myoclonic dementia masquerading as Creutzfeldt-Jakob disease.

We describe a kindred with 7 confirmed and 2 probable cases of subacute dementia accompanied by myoclonus. The inheritance pattern is consistent with autosomal dominance and shows anticipation. The pathological changes involve marked gliosis with neuronal loss of the dorsomedial and midline thalamic nuclei, with lesser involvement of the anterior, lateral, and posterior thalamic nuclei. Medullary olivary hypertrophy is prominent. Spongiform change is minimal or absent. Attempted disease transmission to primates from 3 affected family members has been unsuccessful; Western immunoblot tests have likewise failed to detect the presence of specifically reactive 27-30 kD Mr proteins in brain tissue from 2 of these patients. We conclude that this family has a rare inherited neurological systems degeneration with associated thalamic dementia, the clinical course of which is very similar to Creutzfeldt-Jakob disease.

Adult↗
PubMed1982

Denervation modulated changes in mouse skeletal muscle RNA concentration.

We have examined normal and denervated mouse skeletal muscle for histological evidence of changes in RNA concentration using acridine orange/nucleic acid fluorescence. In denervated muscle, cytoplasmic RNA concentration increases dramatically. The earliest increase is in the subsarcolemmal region, 7 days after denervation. By 28 days after denervation, the increase in RNA is distributed throughout the cytoplasm of the atrophic cells, non-atrophic cells show little or no increase. Prior to the increase in cytoplasmic RNA concentration, many myocyte nuclei exhibit enlarged nucleoli, indicative of active ribosomal RNA synthesis. Such active nucleoli are present throughout the 42 day study period. We conclude that both new RNA synthesis, and preferential accumulation of cytoplasmic RNA are prominent events in denervation atrophy. There is an ordered progression from nucleolar synthesis to subsarcolemmal accumulation to diffuse accumulation in atrophying cells. These observations complement biochemical findings of others which indicate an increase in both RNA and protein synthesis after denervation.

Animals↗
PubMed1982

Oculopharyngeal muscular dystrophy. An autopsied case from the French-Canadian kindred.

We report the complete autopsy findings of a 60-year-old, 12th generation member of the French-Canadian family originally described with oculopharyngeal muscular dystrophy. This report represents the second complete autopsy described in this disease. We show that oculopharyngeal muscular dystrophy is a systemic myopathy with a marked predeliction for extraocular and non-somatically derived muscles. In addition, we present a comprehensive literature review of the disease, including recent therapeutic manipulations to alleviate the major symptoms. Oculopharyngeal muscular dystrophy must be considered as a distinct, well-defined, autosomal dominant systemic myopathy of later life whose etiology remains obscure.

Blepharoptosis↗
PubMed1982

Successful treatment of familial idiopathic lipid storage myopathy with L-carnitine and modified lipid diet.

We describe the clinical presentation, course, pathologic findings, and biochemical abnormalities found in three adult siblings with an idiopathic lipid storage myopathy. The major presenting symptoms were weakness and cramping, which were profound in one patient, moderate in the second patient, and mild in the third. All three individuals exhibited true myotonic discharges on EMG, normal or mildly depressed muscle free carnitine levels, and borderline delayed ketosis (40 hours) with fasting. Muscle biopsies from all three showed neutral lipid storage. Polymorphonuclear leukocytes and macrophages were vacuolated. No systemic abnormalities of glucose or fat metabolism were identified at rest, with fasting, or with exercise. The two more severely affected patients have responded to medium-chain triglyceride diet and oral carnitine with increased strength and muscle bulk and decreased histochemically observed neutral lipid stores in muscle. One patient has had a resolution of the electrical myotonia. Prednisone therapy in one patient resulted in a loss of cramping sensations but not improvement in strength. We suggest that some cases of idiopathic lipid storage myopathy may be safely and effectively treated with carnitine and medium-chain triglyceride diet.

Carnitine↗