A5085434785- Alkaline Phosphatase Research Studies
- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- Biochemical and Molecular Research
- Diet and metabolism studies
- Bone health and osteoporosis research
- Amino Acid Enzymes and Metabolism
- Bone health and treatments
- Vitamin D Research Studies
- Bone and Joint Diseases
- Heterotopic Ossification and Related Conditions
- Muscle metabolism and nutrition
- Selenium in Biological Systems
- Muscle and Compartmental Disorders
- Cancer, Hypoxia, and Metabolism
- Animal Nutrition and Physiology
- Virus-based gene therapy research
- Metabolomics and Mass Spectrometry Studies
- Peroxisome Proliferator-Activated Receptors
- Nutrition, Genetics, and Disease
- Enzyme Structure and Function
- Kidney Stones and Urolithiasis Treatments
- Vitamin C and Antioxidants Research
- Parathyroid Disorders and Treatments
- Antibiotics Pharmacokinetics and Efficacy
Purdue University Fort Wayne
2021-2024
Indiana University – Purdue University Fort Wayne
1976-2018
Purdue University West Lafayette
1962-2011
Indiana University
2009
Indiana University – Purdue University Indianapolis
2005
University of Amsterdam
2005
Shriners Hospitals for Children - St. Louis
2005
Medical College of Wisconsin
2005
Academic Center for Dentistry Amsterdam
2005
St. Joseph Hospital
1983-2003
(R)-Roscovitine (CYC202) is often referred to as a "selective inhibitor of cyclin-dependent kinases." Besides its use biological tool in cell cycle, neuronal functions, and apoptosis studies, it currently evaluated potential drug treat cancers, neurodegenerative diseases, viral infections, glomerulonephritis. We have investigated the selectivity (R)-roscovitine using three different methods: 1) testing on wide panel purified kinases that, along with previously published data, now reaches 151...
Abstract Hypophosphatasia is an inborn error of metabolism characterized by deficient activity the tissue-nonspecific isoenzyme alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization cartilage bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (–/–) had < 1% wild-type plasma activity; heterozygotes predicted mean ∼50%. Phosphoethanolamine, inorganic...
Markedly increased circulating concentrations of pyridoxal-5'-phosphate (PLP) were found in each 14 patients representing all clinical forms hypophosphatasia, an inborn error characterized by deficient activity the tissue nonspecific (bone/liver/kidney) isoenzyme alkaline phosphatase (AP). The mean PLP concentration plasma was 1174 nM (range, 214-3839 nM) and 57 +/- 26 (mean SD) 38 control subjects. In four affected children, urinary excretion degradation product, 4-pyridoxic acid,...
We report a 55-year-old woman who suffered atypical subtrochanteric femoral fractures (ASFFs) after 4 years of exposure to alendronate and then zolendronate given for "osteoporosis." Before treatment, she had low bone mineral density. After several months therapy, metatarsal stress began. Bisphosphonate (BP) administration was stopped following the ASFFs, adult form hypophosphatasia (HPP) diagnosed from serum alkaline phosphatase (ALP) activity, high endogenous levels two natural substrates...
Abstract An 8-month-old girl who seemed certain to die from the infantile form of hypophosphatasia, an inborn error metabolism characterized by deficient activity tissue-nonspecific isoenzyme alkaline phosphatase (TNSALP), underwent first trial bone marrow cell transplantation for this heritable type rickets. After cytoreduction, she was given T-cell-depleted, haplo-identical her healthy sister. Chimerism in peripheral blood and became 100% donor. Three months later, clinically improved,...
Hypophosphatasia features selective deficiency of activity the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP (PALP IALP, respectively) is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], pyridoxal 5'-phosphate [PLP]) accumulate endogenously appear, therefore, to be natural substrates for TNSALP. Carriers hypophosphatasia may have decreased serum elevated substrate levels. To...
Hypophosphatasia (HPP) often leads to premature loss of deciduous teeth, due disturbed cementum formation. We addressed the question what extent and dentin are similarly affected. To this end, we compared teeth from children with HPP those matched controls analyzed them microscopically chemically. It was observed that both acellular cellular formation For dentin, however, no differences in mineral content were recorded. explain dissimilar effects on HPP, assessed pyrophosphate (an inhibitor...
Background: Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease due to deficient activity of the tissue-nonspecific isoenzyme alkaline phosphatase. The infantile form features severe rickets often causing death in first year life from respiratory complications. There no established medical treatment. In 1997, an 8-month-old girl with worsening and life-threatening HPP improved considerably after marrow cell transplantation.
"Perinatal" hypophosphatasia is the most severe form of this inborn error metabolism, which characterized by deficient activity tissue-nonspecific (liver/bone/kidney) isoenzyme alkaline phosphatase (ALP) (TNSALP). We report that autopsy tissue from three affected subjects, was profoundly low in ALP activity, had essentially unremarkable levels pyridoxal-5'-phosphate (PLP), pyridoxal, and total vitamin B6 content despite markedly elevated plasma PLP (5,800, 14,500, 98,500 nM; adult norm,...
The mechanical integrity of bone is dependent on the matrix, which believed to account for plastic deformation tissue, and mineral, elastic deformation. validity this model shown in study based analysis bones vitamin B6-deficient B6-replete chick bones. In model, when control animals are compared, B6 deficiency has no effect mineral content or composition cortical as measured by ash weight (63 ± 6 vs. 58 3); matrix ratio FTIR spectra (4.2 0.6 4.5 0.2), line-broadening analyses X-ray...
Ten nonobese, healthy elderly adults (M = 73.3 years) were monitored polygraphically during sleep for state changes, breathing, and the development of cardiac arrhythmias. All participated in 2 baseline nights 1 night flurazepam 30 mg ingestion; six underwent deprivation; four received ethyl alcohol (.6 mg/kg); whose apnea worsened significantly with pretreated 3 days acetazolamide, taking acetazolamide on fourth night. Elderly an Apnea Index (the number apneas per hour) between 5 7 at...
Abstract Hypophosphatasia (HPP) is the inborn error of metabolism characterized by low serum alkaline phosphatase (ALP) activity caused inactivating mutations within TNSALP, gene that encodes “tissue-nonspecific” isoenzyme ALP (TNSALP). In HPP, extracellular accumulation inorganic pyrophosphate, a TNSALP substrate, inhibits hydroxyapatite crystal growth leading to rickets or osteomalacia. Chronic recurrent multifocal osteomyelitis (CRMO) pediatric syndrome periarticular pain and radiographic...
Natural and artificial manipulation of tissue nonspecific alkaline phosphatase activity indicates that pyrophosphate, phosphoethanolamine, pyridoxal 5′-phosphate are among the natural substrates for this enzyme. Although inorganic phosphate has been recognized as a competitive inhibitor enzyme many years, influence on in serum under physiological conditions not previously reported. We examined kinetics from bovine kidney sera 49 patients with wide range endogenous concentrations using...
We describe four pregnancies in two families which mild hypophosphatasia, apparently transmitted as an autosomal dominant trait, manifested utero severe long bone bowing. Postnatally, there was spontaneous improvement of the skeletal defects. Recognition this presentation for hypophosphatasia by family investigation and assessment fetal skeleton degree ossification chest size using ultrasonography is important. The prognosis condition considerably better than more forms many other disorders...
The aims of this study were to define normal human placental transport pyridoxal, an important form vitamin B6 in pregnancy, and determine the effect short-term alcohol on process. Our studies used isolated single cotyledon from term placenta. Pyridoxal crossed placenta readily both directions, but transfer was a little less than half that antipyrine significantly greater direction fetus. Pyridoxine appeared have similar clearance maternal compartment as intact pyridoxal 5'-phosphate much...
The daily rhythm of plasma tyrosine that occurs in rats fed ad libitum was altered by controlling the time food intake. experimental data suggested (1) absorption from dietary protein and (2) metabolism liver transaminase may be important mechanisms tyrosine. A normal serum occurred human phenylketonuric subjects lacking phenylalanine hydroxylase, so variations hydroxylation to probably do not play a part rhythm. In libitum, there little or no variation phenylalanine, but some changes were...