Minimally Invasive Intradiscal Delivery of BM-MSCs via Fibrous Microscaffold Carriers.

Current treatments of degenerated intervertebral discs often provide only temporary relief or address specific causes, necessitating the exploration of alternative therapies. Cell-based regenerative approaches showed promise in many clinical trials, but limitations such as cell death during injection and a harsh disk environment hinder their effectiveness. Injectable microscaffolds offer a solution by providing a supportive microenvironment for cell delivery and enhancing bioactivity.

Compartment model of neuropeptide synaptic transport with impulse control.

In this paper a mathematical description of a presynaptic episode of slow synaptic neuropeptide transport is proposed. Two interrelated mathematical models, one based on a system of reaction diffusion partial differential equations and another one, a compartment type, based on a system of ordinary differential equations (ODE) are formulated. Processes of inflow, calcium triggered activation, diffusion and release of neuropeptide from large dense core vesicles (LDCV) as well as inflow and diffusion of ionic calcium are represented.

Recurrent unilateral periorbital cellulitis in a pediatric patient--an anatomic abnormality.

A 2-year-old male, otherwise healthy, suffered a total of 7 episodes of recurrent right-sided periorbital celluitis (POC) which began at 11 months of age. Five of the 7 episodes of right eye swelling/erythema required hospital admission for intravenous antibiotics. Imaging studies demonstrated a well-defined dehiscence in the lamina papyracea.

Development of a clinical assay for detection of GAA mutations and characterization of the GAA mutation spectrum in a Canadian cohort of individuals with glycogen storage disease, type II.

Glycogen storage disease, type II (GSDII; Pompe disease; acid maltase deficiency) is an autosomal recessive disease caused by mutations of the GAA gene that lead to deficient acid alpha-glucosidase enzyme activity and accumulation of lysosomal glycogen. Although measurement of acid alpha-glucosidase enzyme activity in fibroblasts remains the gold standard for the diagnosis of GSDII, analysis of the GAA gene allows confirmation of clinical or biochemical diagnoses and permits predictive and prenatal testing of individuals at risk of developing GSDII. We have developed a clinical molecular test for the detection of GAA mutations based on cycle sequencing of the complete coding region.

Diagnosis of Krabbe disease by use of a natural substrate.

This chapter describes in detail a practical procedure for the preparation of radiolabeled galactocerebroside and its use in the assay of galactocerebrosidase (GalCase), the enzyme deficient in globoid cell leukodystrophy (Krabbe disease). The reference range for leukocytes and fibroblasts is 0.9-4.

Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease.

Primary deficiency of beta-galactosidase results in GM1 gangliosidosis and Morquio B disease. Of the more than 40 disease-causing mutations described in the Gal gene to date, about 75% are of the missense type and are scattered along the length of the gene. No single, major common mutation has been associated with GM1 gangliosidosis.

Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up.

Galactosialidosis (GS) is an autosomal recessive condition caused by combined deficiency of the lysosomal enzymes beta-galactosidase and alpha-neuraminidase. The combined deficiency has been found to result from a defect in protective protein/cathepsin A (PPCA), an intralysosomal protein which protects these enzymes from premature proteolytic processing. The most severe form of GS, the early-infantile form, results in early onset of edema, ascites, visceromegaly, and skeletal dysplasia.

Homozygous presence of the crossover (fusion gene) mutation identified in a type II Gaucher disease fetus: is this analogous to the Gaucher knock-out mouse model?

Gaucher disease (GD) is an inherited deficiency of beta-glucocerebrosidase (EC 3.1.2.

Genotype-phenotype pitfalls in Gaucher disease.

Gaucher disease (GD), caused by inherited deficiency of beta-glucocerebrosidase (beta-Glc, EC 3.1.2.

Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl.

The mechanism of profound generalized iduronate sulfatase (IDS) deficiency in a developmentally delayed female with clinical Hunter syndrome was studied. Methylation-sensitive RFLP analysis of DNA from peripheral blood lymphocytes from the patient, using MspI/HpaII digestion and probing with M27 beta, showed that the paternal allele was resistant to HpaII digestion (i.e.

Multiple sulfatase deficiency with early severe retinal degeneration.

We report an unusual case of multiple sulfatase deficiency in which neurodegeneration was accompanied by early, severe visual impairment associated with prominent pigmentary retinopathy, suggesting a diagnosis of neuronal ceroid-lipofuscinosis. The levels of arylsulfatases A, B, and C, heparan N-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, and iduronate-2-sulfate sulfatase were all markedly decreased in cultured skin fibroblasts. Screening tests for mucopolysacchariduria were consistently negative; however, thin-layer chromatographic analysis of isolated urinary glycosaminoglycans showed increased amounts of heparan sulfate.

First trimester prenatal diagnosis of Tay-Sachs disease using the sulfated synthetic substrate for hexosaminidase A.

Uncultured and cultured embryonic trophoblastic tissue obtained by chorionic villus sampling (CVS) displays enzyme activity towards 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranosyl-6-sulfate (MUGS), a specific substrate for Hexosaminidase A (Hex A), the enzyme deficient in Tay-Sachs disease (TSD). Specific activity is comparable to that found in cultured amniocytes and fibroblasts. The enzyme activity has a pH optimum of 4.

Screening for carriers of Tay-Sachs disease among Ashkenazi Jews. A comparison of DNA-based and enzyme-based tests.

Background And Methods: The prevention of Tay-Sachs disease (GM2 gangliosidosis, type 1) depends on the identification of carriers of the gene for this autosomal recessive disorder. We compared the enzyme-based test widely used in screening for Tay-Sachs disease with a test based on analysis of DNA. We developed methods to detect the three mutations in the HEXA gene that occur with high frequency among Ashkenazi Jews: two mutations cause infantile Tay-Sachs disease, and the third causes the adult-onset form of the disease.

Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl.

A female child of healthy, unrelated parents presented at 12 months of age with a history of moderately severe developmental delay, macrocephaly, dysmorphic facies, hypotonia, hepatosplenomegaly, mild generalized dysostosis multiplex, mucopolysacchariduria (dermatan and heparan sulfates), and Alder-Reilly bodies in peripheral blood leukocytes. Iduronate sulfatase activity in plasma was markedly depressed: 0.11 units/ml/h (normal, 1.

Tay-Sachs disease carrier screening: follow-up of a case-finding approach.

In order to determine the status of Tay-Sachs disease carrier identification in Toronto, Canada, since a change was made in 1978 from testing in the context of large-scale community clinics (up to 1,200 individuals tested in 1 day) to a case-finding approach to screening, a sample of area Jews was surveyed by questionnaire. The results indicated that a trend has developed for individuals at risk to delay testing until pregnancy when carrier detection is technically more difficult and the time available for retesting and organizing prenatal diagnosis is limited. If the trend continues, the full potential of chorionic villus sampling (CVS) for the prenatal diagnosis of the disease will be difficult to realize.

Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy.

In a child with enzymatically and histopathologically proven metachromatic leukodystrophy (MLD), the disease pursued a course typical of juvenile MLD characterized by neurological degeneration beginning at age 9 years and ending in death at age 18. A younger brother of the patient was found to have profound deficiency of arylsulfatase A in leukocytes and to excrete five- to 20-fold greater-than-normal amounts of sulfatide in the urine. He was completely free of symptoms attributable to MLD until age 16 when he developed acute cholecystitis caused by sulfatide accumulation in the gallbladder.

Simultaneous fractionation of four placental neutral glycosphingolipids with a continuous gradient.

We describe a method for isolating milligram quantities of the four neutral glycosphingolipids, glucocerebroside, lactosylceramide, traiosylceramide, and globoside, from human placental tissue. This procedure is carried out on a silicic acid column eluted with a continuous chloroform-methanol gradient (19:1 to 4:1); the four glycosphingolipids elute as separate fractions with no need for further separation. The method is simple, rapid, and yields sufficient material to use as analytical standards for several hundred runs.

HPLC analysis of urinary sulfatide: an aid in the diagnosis of metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) presents as six separate variant forms, four allelic and two non-allelic. It is diagnosed in the laboratory by a decrease in the fibroblast or leukocyte arylsulfatase A activity, generally against an artificial substrate. Since residual enzyme activity is not always an indicator of presence or absence of disease, it may be helpful to supplement this information with that of the presence or absence of sulfatide storage in the body.

HPLC analysis of neutral glycolipids: an aid in the diagnosis of lysosomal storage disease.

Concentrations of GL-la (glucocerebroside) (8.36 nmol/ml), GL-2a (lactosylceramide) (4.03 nmol/ml), GL-3a (globotriosylceramide) (2.

Type 2 GM1 gangliosidosis with long survival and neuronal ceroid lipofuscinosis.

Neurologic deterioration began in a girl before age 2 years. By 4 she was spastic and decerebrate. GM1 gangliosidosis was diagnosed by absence of beta-galactosidase activity in leukocytes and fibroblasts.