Clinical, genetic, and structural characterization of a novel TUBB4B tubulinopathy.

Microtubules are cytoskeletal polymers of ⍺/β-tubulin heterodimers essential for a wide range of cellular processes. Pathogenic variations in microtubule-encoding genes (e.g.

Newborn Screening: Review of its Impact for Cystinosis.

Newborn screening (NBS) programmes are considered to be one of the most successful secondary prevention measures in childhood to prevent or reduce morbidity and/or mortality via early disease identification and subsequent initiation of therapy. However, while many rare diseases can now be detected at an early stage using appropriate diagnostics, the introduction of a new target disease requires a detailed analysis of the entire screening process, including a robust scientific background, analytics, information technology, and logistics. In addition, ethics, financing, and the required medical measures need to be considered to allow the benefits of screening to be evaluated at a higher level than its potential harm.

Nephropathic Cystinosis: A Distinct Form of CKD-Mineral and Bone Disorder that Provides Novel Insights into the Regulation of FGF23.

Background: The rare lysosomal storage disease nephropathic cystinosis presents with renal Fanconi syndrome that evolves in time to CKD. Although biochemical abnormalities in common causes of CKD-mineral and bone disorder have been defined, it is unknown if persistent phosphate wasting in nephropathic cystinosis is associated with a biochemical mineral pattern distinct from that typically observed in CKD-mineral and bone disorder.

Methods: We assessed and compared determinants of mineral homeostasis in patients with nephropathic cystinosis across the predialysis CKD spectrum to these determinants in age- and CKD stage-matched patients, with causes of CKD other than nephropathic cystinosis.

Management of bone disease in cystinosis: Statement from an international conference.

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome.

Skeletal Consequences of Nephropathic Cystinosis.

Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite the multiple risk factors for bone disease, the frequency and severity of skeletal disorders in nephropathic cystinosis have not been described.

Cystinosis: renal glomerular and renal tubular function in relation to compliance with cystine-depleting therapy.

Background And Objectives: Nephropathic cystinosis is a lysosomal storage disorder characterized by renal tubular Fanconi syndrome in infancy and glomerular damage leading to renal failure at ∼10 years of age. Therapy with the cystine-depleting agent cysteamine postpones renal failure, but the degree of compliance with this treatment has not been correlated with preservation of kidney function.

Methods: We assessed leucocyte cystine depletion by cysteamine and created the composite compliance score that incorporates the extent of leucocyte cystine depletion, as well as duration of cysteamine treatment, into a single integer.

Nephropathic cystinosis: an international consensus document.

Cystinosis is caused by mutations in the CTNS gene (17p13.2), which encodes for a lysosomal cystine/proton symporter termed cystinosin. It is the most common cause of inherited renal Fanconi syndrome in young children.

1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis.

Background And Objectives: Elevated serum vitamin D with hypercalciuria can result in nephrocalcinosis and nephrolithiasis. This study evaluated the cause of excess 1,25-dihydroxycholecalciferol (1α,25(OH)2D3) in the development of those disorders in two individuals.

Design, Setting, Participants, & Measurements: Two patients with elevated vitamin D levels and nephrocalcinosis or nephrolithiasis were investigated at the National Institutes of Health (NIH) Clinical Center and the NIH Undiagnosed Diseases Program, by measuring calcium, phosphate, and vitamin D metabolites, and by performing CYP24A1 mutation analysis.

Cystinosis: the evolution of a treatable disease.

Cystinosis is a rare autosomal recessive disorder involving lysosomal storage of the amino acid cystine due to a defect in the membrane transport protein, cystinosin. Since the introduction of kidney transplants and the availability of cystine-depleting medical therapy, this previously fatal disease was transformed into a treatable disorder. Renal allografts and medical therapy targeting the basic metabolic defect have altered the natural hisotry of cystinosis so drastically that patients have a life expectancy extending past 50 years.

Discordance in interpretation of chest radiographs between pediatric intensivists and a radiologist: impact on patient management.

Purpose: When radiologists are not available, chest radiographs (CXRs) of pediatric intensive care unit (PICU) patients are commonly interpreted by pediatric intensivists. We prospectively investigated the frequency of errors in CXR interpretation by pediatric intensivists and their impact on patient management.

Materials And Methods: Chest radiographs of PICU patients were evaluated by 5 pediatric intensivists then by a pediatric radiologist (the "gold standard").

Hypocalcemia in a patient with osteosarcoma and 22q11.2 deletion syndrome.

Hypocalcemia is a rare complication of osteosarcoma, having been described in only 4 reports. We present the case of a 16-year-old male with metastatic osteosarcoma of the right humerus who was found to have severe asymptomatic hypocalcemia. Cytogenetic analysis of peripheral blood revealed a microdeletion in band 22q11.

Nephropathic cystinosis: late complications of a multisystemic disease.

Cystinosis is a rare autosomal recessive disorder due to impaired transport of cystine out of cellular lysosomes. Its estimated incidence is 1 in 100,000 live births. End-stage renal disease (ESRD) is the most prominent feature of cystinosis and, along with dehydration and electrolyte imbalance due to renal tubular Fanconi syndrome, has accounted for the bulk of deaths from this disorder.

Safety and immunogenicity of a prototype enterotoxigenic Escherichia coli vaccine administered transcutaneously.

Transcutaneous immunization (TCI) is a new method for vaccine delivery that has been shown to induce immunity relevant to enteric disease vaccines. We evaluated the clinical safety and immunogenicity of a recombinant subunit vaccine against enterotoxigenic Escherichia coli (ETEC) delivered by TCI. Adult volunteers received patches containing the recombinant ETEC colonization factor CS6, either with heat-labile enterotoxin (LT) or patches containing CS6 alone.

[Fundamental and applied aspects of research on the virus-like plasmids of the yeast Saccharomyces].

Six types of the antagonistic activity (AA) in Saccharomyces were distinguished and characterized. The K1, K2, K3 and K6 activities were associated with the presence of the two kinds of cytoplasmic killer virus-like particles (VLP)--cytoplasmic double-stranded RNAs (dsRNAs) consisting of the main (L) and minor (M) species. All four antagonistic groups contained the L dsRNAs of the same size.

[Chromosome polymorphism in the yeast Saccharomyces].

The variability of chromosomal band patterns was determined by pulse electrophoresis. The natural strains differed by the quantity and electrophoretic mobility of chromosomal DNA bands. The strains of independent genetic stocks originated from the XII race of Saccharomyces cerevisiae showed less significant difference in band patterns than the strains of different species of the Saccharomyces genus.

[UV-spectrophotometry in drug control. 47. Drug substances with chromophores and auxochromes in cyclic and tricyclic systems (benzodiazepine, dibenzoazepine and dibenzodiazepine)].

The results of a systematic examination of the UV/VIS spectra of 10 drug substances with chromophores and auxochromes in bicyclic and tricyclic systems (benzodiazepine, dibenzoazepine and dibenzodiazepine) are described. Influences of substituents and solvents on shifts of the E, K, B and R bands are discussed.

[Genetic strains of Hansenula polymorpha].

Six centromeric linkage groups and four non-centromeric fragments are revealed in the genetic stocks of Hansenula polymorpha which were obtained by intratetrad breeding in several generations of two genetically different parental strains progeny. Fourteen nuclear markers are mapped, including auxotrophic mutations, mating regulation loci, determinants of sporulation and heat tolerance. Complex origin of the haploid genome of these stocks leads to affinity interactions and to 14 per cent increase in DNA content in haploid stocks, as compared with the parental strains.

[Genetic control of the number of copies of type K2 killer plasmids in Saccharomyces cerevisiae].

13 non-linked chromosomal mutations derepress the negative genetic control of copy number of K2 yeast killer plasmids and lead to 1.5-2-fold elevating of copy number of that type plasmids -L2A and M2 virus-like dsRNA. The content of both plasmids is increased 3-5-fold in cells with chromosomal ski5 mutation, as compared to the strains of wild type.

[A new type of antagonistic activity of Saccharomycetes yeasts and its mode of inheritance].

New type of killer activity of Saccharomyces cerevisiae was found. About 40% of this yeast strains tested formed growth inhibition zones on the lawn of the sensitive yeast Pachysolen tannophilus (Boldin et Adzet) BKM y-274. As shown by crossing these killers with non-killers and the tetrad analysis of hybrids obtained, 2 killer: 2 non-killer segregation took place, indicating the chromosomal mode of inheritance of the character.

[Killer systems of Saccharomyces cerevisiae yeasts].

The killer systems of Saccharomyces cerevisiae are a peculiar group of cytoplasmic symbionts of primitive eukaryotes. The genetic material of these symbionts is double-stranded RNA. Their basic properties are linearity of genome, its fragmentation, resulting in two separately replicating major and minor segments, and the ability to control the synthesis of secretory proteins--mycocins which can kill the taxonomically related strains.

[Transformation of the yeast Hansenula polymorpha by a hybrid plasmid containing the fragment of host DNA].

Spheroplasts of Hansenula polymorpha strain deficient in 2-isopropylmalate dehydrogenase have been shown to be transformed by the DNA of a hybrid plasmid pHRI, carrying the LEU2 gene from S. cerevisiae and 2.0 kilobase HindIII fragment of H.

[Nuclear mutants of Saccharomyces cerevisiae K2 yeasts with decreased killer activity].

Recessive mutations in two chromosomal unlinked genes kir1 and kir2 of Saccharomyces cerevisiae K2 result in weak killer activity or in complete loss of killer capacity. Kir1 is located on chromosome 7 and is linked to ade7 and ski6. The kir1 and kir2 mutants reveal no alteration of cell membrane.

[Interferon-inducing and antiviral activity of dsRNA of yeast origin].

The paper describes derivation of double-stranded RNA from K plasmid of Sachcaromyces cerevisiae yeast by means of electrophoresis in agar gel and by differential salting out with 4 M lithium chloride. Studies in vitro and in vivo demonstrated a high interferon-inducing and antiviral activity of dsRNA preparations from the yeast plasmid.

["Killer" plasmid mutants obtained by exposure to 5-fluorouracil].

Weak killers were tolerated from a killer strain of type k2 of Saccharomyces cerevisiae by treatment with 5-fluorouracil. They segregated sensitive clones during vegetative growth with a frequency from 2 to 20 per cent (nonstable killers, Knst mutants). Alteration of killer activity in these mutants is the result of a mutation in the cytoplasmic killer determinant (KIL-k).