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Biomedical subjects

L S Wolfe

Publications and source records attributed to L S Wolfe.

At least 37 records · Page 2Linked to original sources
PubMed1988

Dolichol and dolichyl phosphate in the neuronal ceroid-lipofuscinoses and other diseases.

Although, compared to age-matched control samples, nonphosphorylated dolichols are significantly increased in the cerebral cortex of children with the late infantile and juvenile types of neuronal ceroid-lipofuscinosis (NCL), dolichyl phosphates are increased to a much greater extent in infantile, late infantile, and juvenile forms of this disease group. Dolichyl phosphates in the cerebral cortex, expressed as a percentage of the combined nonphosphorylated and phosphorylated compounds, ranged from 59 to 85 (mean 71) in NCL, whereas in the non-NCL disease group the range is 18-36 (mean 25). This marked proportional increase in dolichyl phosphates is not unique to NCL but is also found in the brain of GM1-gangliosidosis and Tay-Sachs disease patients. In the liver from NCL patients, dolichyl phosphates are not a major proportion of the total dolichol compounds (1-9%). However, in the kidney and heart, dolichyl phosphates are again markedly increased, and this is associated with large storage of ceroid. Although to a lesser extent than in NCL, dolichols and dolichyl phosphates are significantly increased over levels in age-matched control samples in the temporal cortex in Alzheimer disease. Our interpretation of these results is that storage in secondary in secondary lysosomes in NCL and the gangliosidoses leads to a decrease in the catabolism of dolichyl phosphate compounds in the Golgi saccules or primary lysosomes.

Alzheimer Disease↗
PubMed1988

Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency.

Two sisters presented with progressive muscle cramps, as well as wasting and weakness of the legs with onset after age 20. They also showed intention tremor of the upper extremities and dysarthria starting during the first decade. The older patient also had fasciculations; the younger, hyperreflexia. Total plasma beta-hexosaminidase (Hex) activity with 4-methylumbelliferyl-acetyl-glucosamine as substrate was reduced to 1.4% and 2.7% of the control in the 2 patients, respectively. Hex A activity measured by 4-methylumbelliferyl-N-acetylglucosamine-6-O-sulphate as substrate was 9.9% and 12.8% of the mean control value in the 2 patients, respectively. Hex B activity was undetectable in both patients. Leukocyte total Hex activity was 7-8% of normal; residual Hex A activity in the 2 patients was 17.8% and 16.3% of normal controls, respectively. Fibroblastic residual Hex A activity in the 2 patients was 9.6% and 22% of normal mean value, respectively. Appendiceal ganglion cells contained membranous cytoplasmic bodies in the younger patient. Thin layer chromatography of the appendiceal extract from one patient (III/2) showed a marked increase of GM2 ganglioside, and some increase of GM3 ganglioside. Northern blots performed on fibroblast cell lines from both patients for the demonstration of alpha and beta locus messenger RNA showed no difference between patients and control. These patients have a rare form of adult-onset progressive motor neuron disease presumably due to abnormal beta subunits, causing severe deficiency of both Hex A and Hex B. The phenotypic expression of this disease is similar to motor neuron disease due to alpha locus mutations, which suggests that the Hex A deficiency, even though only a partial one, may be the important pathogenic factor.

Adult↗
PubMed1988

Kufs' disease: a critical reappraisal.

A review of 118 cases published as Kufs' disease revealed only 50 cases, including 2 patients described herein, that fulfilled our criteria for this diagnosis. Of the other 68 cases, 16 had inadequate data for analysis, 21 had evidence of a storage disease other than Kufs' disease, 10 did not have clear evidence of any neuronal storage, and 21 had atypical clinical features considered outside the spectrum of Kufs' disease. The 50 cases accepted as Kufs' disease comprised two clinical phenotypes; progressive myoclonus epilepsy (Type A) and dementia with motor disturbances (Type B). Marked photosensitivity was a striking feature of some Type A cases, and facial dyskinesias were common amongst Type B patients. Onset was typically at around the age of 30 years. A few cases began in adolescence; these differ from the protracted juvenile form of neuronal ceroid-lipofuscinosis by the absence of visual failure. Demonstration of fingerprint profiles or granular osmiophilic deposits by electron microscopy is mandatory for definitive diagnosis. Urinary sediment dolichol levels were markedly elevated in our 2 cases. This biochemical finding confirms the relationship of Kufs' disease to the early forms of neuronal ceroid-lipofuscinosis and is consistent with our hypothesis that these diseases are due to defects in the intracellular processing of lysosomal and related membranes.

Adult↗
PubMed1987

Elevated urinary dolichol excretion in the Hermansky-Pudlak syndrome. Indicator of lysosomal dysfunction.

The Hermansky-Pudlak syndrome, a triad of albinism, platelets lacking dense bodies, and storage of ceroid-like material in tissues, occurs approximately once in 2,000 northwestern Puerto Ricans. The manifestations of storage disease are variable and include granulomatous colitis, restrictive lung disease, kidney failure, and cardiomyopathy. The autofluorescent material stored in the Hermansky-Pudlak syndrome is histochemically similar to that stored in neuronal ceroid/lipofuscinosis. The material in neuronal ceroid/lipofuscinosis contains dolichols, which are components of lysosomes, and patients show increased urinary excretion of dolichols. This study of 49 patients with the Hermansky-Pudlak syndrome found that urinary dolichol levels are increased in those patients with evidence of ceroid storage in the kidneys but are not elevated when storage occurs in tissues other than the kidneys. The excretion of ceroid was not influenced by the saturation state of dietary fat. A defect in processing of membranes of lysosomes, melanosomes, and dense bodies may be involved in the syndrome.

Albinism↗
PubMed1986

Urinary sediment dolichols in the diagnosis of neuronal ceroid-lipofuscinosis.

Long-chain polyisoprenol alcohol (dolichols) levels are significantly increased in the urinary sediment of patients with infantile, late-infantile, and juvenile forms of neuronal ceroid-lipofuscinosis (NCL). The values in obligate heterozygotes for these diseases are similar to those in patients with other neurological diseases and in healthy controls. Antioxidant treatment of patients with juvenile NCL has no effect on dolichol values. The rate of false-negative results is 13.9% in infantile, 7.5% in late-infantile, and 15.0% in juvenile NCL. False-positive results were found in 8.2 to 14.3% of patients with other neurological diseases and in 15.4% of healthy controls. The test is of considerable value in the diagnosis of NCL and in decisions on whether to perform a biopsy. It is not useful in the screening of random samples, however.

Adolescent↗
PubMed1985

Hexosaminidase-A deficiency presenting as atypical juvenile-onset spinal muscular atrophy.

Three patients from two families had an unusual phenotypical variant of late-onset hexosaminidase-A deficiency. The clinical picture was dominated by spinal motor neuron involvement mimicking juvenile-onset spinal muscular atrophy. Atypical features included prominent muscle cramps, postural and action tremor, recurrent psychosis, incoordination, corticospinal and corticobulbar involvement, and dysarthria. The presence of these atypical features in patients whose lower motor neuron involvement would otherwise be consistent with juvenile-onset spinal muscular atrophy should raise the suspicion of the presence of hexosaminidase-A deficiency and GM2 gangliosidosis that can be proved by appropriate enzyme assays.

Adult↗
PubMed1985

Ca2+ depletion-induced disconnection of tight junctions in isolated rat brain microvessels.

Cerebral microvessels were isolated from rat brains. One part of the microvessel pellets was incubated for 25 or 90 min in Krebs-Henseleit bicarbonate buffer (KHB) at pH 7.5 (control group). The other part of the pellets was treated for the same periods of time with Ca2+-free KHB, containing 2.2 mM EGTA and 2 mM glucose (experimental group). Morphological changes of endothelial tight junctions were evaluated in 100 randomly selected interendothelial clefts from isolated cerebral microvessels of each groups by electron microscopy. Following 25 min of incubation time, either with Ca2+-containing or with Ca2+-free KHB, no significant changes of tight junctions were observed. After 90 min of incubation in Ca2+-free medium, 58% of tight junctions were altered (in 42% partial, and in 16% complete disconnection of tight junctions were found). This contrasted the control group, where only 14% of tight junctions were disconnected (12% partially and 2% completely). Our results are consistent with a role for intercellular Ca2+ in maintaining structural integrity of cerebral tight junctions.

Animals↗
PubMed1985

Phosphatidylcholine and 4-methylumbelliferyl phosphorylcholine hydrolysis by purified placental sphingomyelinase.

We present evidence which indicates that highly purified placental acid sphingomyelinase hydrolyses [14C]phosphatidylcholine [( 14C]PC) and the synthetic phosphodiester 4-methylumbelliferyl phosphorylcholine (4-MUPC). Hydrolysis was achieved by phospholipase C phosphodiesterase action. Of the several detergents tested, sodium taurocholate alone was necessary for PC hydrolysis, while 4-MUPC was hydrolysed independent of any detergent requirement. The pH optima for the reactions were 4.6-4.8 for PC hydrolysis and 4.8-5.0 for 4-MUPC hydrolysis. As with sphingomyelin hydrolysis, degradation of both PC and 4-MUPC was inhibited by 5'-, 3'-, and 2'-AMP, 5'-AMP being the most effective of the three. Furthermore, the phosphodiesterase activity against PC and 4-MUPC copurified with sphingomyelinase from human placenta and cross-reacted with a specific anti-sphingomyelinase monoclonal antibody, strongly indicating identity of the phosphodiesterases. This explains phospholipase C deficiency in sphingomyelinase-deficient Niemann-Pick disease cells.

Adenine Nucleotides↗
PubMed1985

Dolichols are elevated in brain tissue from Alzheimer's disease, but not in urinary sediment from Alzheimer's disease and Down's syndrome.

Long-chain polyisoprenoid alcohols (dolichols) were measured in different brain regions dissected postmortem from 26 histopathologically confirmed cases of Alzheimer's disease and 24 age-matched nonAlzheimer control patients. They were significantly elevated in all parts of the cerebrum, but not in the cerebellum, of Alzheimer patients. The highest values were found in the temporal cortex and hippocampus. Out of the individual dolichol molecular species, the one with the most isoprene units (C105) was significantly increased in the temporal cortex, hippocampus, and basal forebrain of Alzheimer patients, compared with the controls. Dolichols were normal in the urinary sediment of 10 Alzheimer patients and nine patients with Down's syndrome, in comparison to age-matched controls for both groups. This is in contrast to neuronal ceroid-lipofuscinosis patients in whom dolichols are elevated in cerebral cortex, as well as in the cells of the urinary sediment, indicating generalized ceroid-lipofuscin storage.

Aged↗
PubMed1985

Diagnostic value of kidney biopsy in heterozygous Fabry's disease.

We studied a case of abnormal renal pathologic findings in a female patient that were suggestive of Fabry's disease. Except for corneal clouding, no other clinical findings were consistent with this diagnosis. The serum and urinary enzyme levels were all within normal limits; the ceramide trihexoside level was slightly increased in the urine. We examined the pathologic changes in the context of the present knowledge of renal lesions in storage diseases.

Adult↗