Correction to: Neurological Symptoms in Hypophosphatasia.

Due to a typesetting error the title of the article was published wrongly.

Neurological symptoms in Hypophosphatasia.

Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options. INTRODUCTION: Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP. METHODS: A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms. RESULTS: Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%. CONCLUSIONS: The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.

Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: Recommendations from the international Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium.

Radiation exposure to the thyroid gland during treatment of childhood, adolescent and young adult cancer (CAYAC) may cause differentiated thyroid cancer (DTC). Surveillance recommendations for DTC vary considerably, causing uncertainty about optimum screening practices. The International Late Effects of Childhood Cancer Guideline Harmonization Group, in collaboration with the PanCareSurFup Consortium, developed consensus recommendations for thyroid cancer surveillance in CAYAC survivors. These recommendations were developed by an international multidisciplinary panel that included 33 experts in relevant medical specialties who used a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. Of the two available surveillance strategies, thyroid ultrasound and neck palpation, neither was shown to be superior. Consequently, a decision aid was formulated to guide the health care provider in counseling the survivor. The recommendations highlight the need for shared decision making regarding whether to undergo surveillance for DTC and in the choice of surveillance modality.

Hamster polyomavirus infection in a pet Syrian hamster (Mesocricetus auratus).

An approximately 8-week-old pet Syrian hamster (Mesocricetus auratus) with a 1-week history of dyspnea, hyporexia, and ataxia was submitted for necropsy. On gross examination, the hamster had multiple abdominal adhesions and enlargement of the mesenteric lymph node. Histologic evaluation revealed multicentric lymphoma of the liver, jejunum, mesenteric lymph node, testicular fat pad, and epididymis. Based on the hamster's age and the type and distribution of the lymphoma, a presumptive diagnosis of hamster polyomavirus-induced lymphoma was made. A specific polymerase chain reaction (PCR) was developed, which confirmed the diagnosis. An in situ PCR demonstrated hamster polyomavirus DNA within lymphocytes of the multicentric lymphoma and renal tubular epithelial cells and within clusters of enterocytes in the jejunum. These data are consistent with environmental dissemination of hamster polyomavirus virions through the renal tubular epithelium and into the urine and with fecal shedding of hamster polyomavirus virions; however, additional studies will be needed to confirm these observations.

Treatment of REM sleep behavior disorder with donepezil: a report of three cases.

Three patients with REM behavior disorder whose nocturnal symptoms were markedly improved by treatment with the acetylcholinesterase inhibitor donepezil are reported. Donepezil may have a role in the treatment of REM behavior disorder, possibly through its actions on cholinergic pathways in the brainstem.

Helicobacter mesocricetorum sp. nov., A novel Helicobacter isolated from the feces of Syrian hamsters.

A spiral-shaped bacterium with bipolar, single, nonsheathed flagella was isolated from the feces of Syrian hamsters. The bacterium grew as a thin spreading film at 37 degrees C under microaerobic conditions, did not hydrolyze urea, was positive for catalase and alkaline phosphatase, reduced nitrate to nitrite, did not hydrolyze hippurate, and was sensitive to nalidixic acid but resistant to cephalothin. Sequence analysis of the 16S rRNA gene and biochemical and phenotypic criteria indicate that the novel bacterium is a helicobacter. The novel bacterium is most closely related to the recently described mouse enteric helicobacter, Helicobacter rodentium. This is the first urease-negative Helicobacter species with nonsheathed flagella isolated from feces of asymptomatic Syrian hamsters. We propose to name this novel helicobacter Helicobacter mesocricetorum. The type strain is MU 97-1514 (GenBank accession number AF072471).

Diagnostic sleep testing in the evaluation of snoring and sleep apnea.

The dilemma frequently encountered by the dentist wishing to offer an appliance for treatment of snoring or sleep apnea is whether there is a need for extensive testing of patients who present with a complaint of snoring. This article describes diagnostic sleep testing in the evaluation of patients with snoring and sleep apnea.

Analysis of the tricho-dento-osseous syndrome genotype and phenotype.

The tricho-dento-osseous (TDO) syndrome demonstrates kinky curly hair, thin-pitted enamel, taurodontism, and thickening of cortical bone. The purpose of this investigation was to characterize the phenotypic variation of TDO in 3, previously unreported, kindreds and to examine possible candidates for the genomic TDO locus. Thirty-three affected and 20 unaffected individuals were recruited for prospective analysis. Participants were evaluated clinically and photographed by one examiner. Blood was drawn for genetic linkage analyses and radiographs were taken to assess dental and skeletal characteristics. All TDO individuals with teeth had generalized thin and/or pitted enamel hypoplasia. Taurodontism was present in all affected individuals, but was variably expressed. Unique kinky/curly hair at birth was reported in 85% of affected individuals. The curly hair phenotype was retained in 46% of affected individuals after infancy. Thick cranial bones, lack of visible pneumatization of the mastoid process, and/or obliteration of the calvarial diploë was seen in 97% of affected persons compared with 30% of the unaffected individuals. The findings suggest that curly hair at birth, enamel hypoplasia, and taurodontism are highly penetrant yet clinically variable components of TDO. The ABO, Kell, and Gc loci previously suggested to be linked to TDO were excluded as candidates in this TDO population. This investigation characterizes the marked variability in the expression of skeletal, hair, and dental manifestations. The broad range of TDO phenotypes seen in these families, including a variety of skeletal changes, does not support subdividing TDO into multiple subtypes based on subtle phenotypic differences.

Determination of the carbon monoxide binding constants of myoglobin mutants: comparison of kinetic and equilibrium methods.

The carbon monoxide (CO) binding constants of human myoglobin (Mb) and several single-site mutants have been determined using two different methods. In the kinetic method, which is commonly used for this ligand, the overall association (k(on)) and dissociation (k(off)) rates of CO were measured by flash photolysis and NO replacement, respectively, and the ratio k(on)/k(off) was calculated. In the equilibrium method, the binding constant Keq was measured directly using a thin-layer technique. These two measurements yield similar results for human wild-type Mb but differ significantly for some of the mutants. Possible reasons for these discrepancies are analyzed. A model assuming the presence of interconverting conformers with different association and dissociation rates is considered in light of infrared measurements on the CO stretching frequency in the MbCO forms of the same proteins [Balasubramanian et al. (1993a) Proc. Natl. Acad. Sci, U.S.A. 90, 4718]. It is suggested that in the case of some mutants which exhibit multiple conformations, this model may lead to nonequilibrium kinetics, which could produce the observed discrepancies between the kinetic and equilibrium determinations of the binding constant. These results suggest that both equilibrium and kinetic data should be obtained, even for a monomeric protein such as Mb, before the relative stabilities of mutants can be meaningfully compared.

Photosensitivity of solgel-derived germanosilicate planar waveguides.

The effects of controlled atmosphere heat treatments on the photosensitivity and UV absorption of GeO(2)-SiO(2) solgel planar waveguides are presented. Photoinduced refractive-index changes in the samples are deduced from photosensitive grating writing experiments and are found to be of the order of those seen in some fiber experiments. A correlation is seen between the sample sensitivity and the strength of the absorption at 242 nm, providing insight into the possible mechanisms governing photosensitive processes in these materials.

A dodecamer of globin chains is the principal functional subunit of the extracellular hemoglobin of Lumbricus terrestris.

Repeated dissociation of the approximately 3600-kDa hexagonal bilayer extracellular hemoglobin of Lumbricus terrestris in 4 M urea followed by gel filtration at neutral pH produces a subunit that retains the oxygen affinity of the native molecule (approximately 12 torr), but only two-thirds of the cooperativity (nmax = 2.1 +/- 0.2 versus 3.3 +/- 0.3). The mass of this subunit was estimated to be 202 +/- 15 kDa by gel filtration and 202 +/- 26 kDa from mass measurements of unstained freeze-dried specimens by scanning transmission electron microscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of this subunit showed that it consists predominantly of the heme-containing subunits M (chain I, 17 kDa) and T (disulfide-bonded chains II-IV, 50 kDa). Mixing of subunits M and T isolated concurrently with the 200-kDa subunit resulted in partial association into particles that had a mass of 191 +/- 13 kDa determined by gel filtration and 200 +/- 38 kDa determined by scanning transmission electron microscopy and whose oxygen affinity and cooperativity were the same as those of the 200-kDa subunit. The results imply that the 200-kDa subunit is a dodecamer of globin chains, consisting of three copies each of subunits M and T (3 x chains (I + II + III + IV], in good agreement with the mass of 209 kDa calculated from the amino acid sequences of the four chains, and represents the largest functional subunit of Lumbricus hemoglobin. Twelve copies of this subunit would account for two-thirds of the total mass of the molecule, as suggested earlier (Vinogradov, S. N., Lugo, S. L., Mainwaring, M. G., Kapp, O. H., and Crewe, A. V. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 8034-8038). The retention of only partial cooperativity by the 200-kDa subunit implies that full cooperativity is dependent on the presence of a complete hexagonal bilayer structure, wherein 12 200-kDa subunits are linked together by approximately 30-kDa heme-deficient chains.

Optical properties of sol-gel spin-coated TiO(2) films and comparison of the properties with ion-beam-sputtered films.

Transparent and optical-grade TiO(2) coatings were prepared by sol-gel spinning and ion-beam sputtering techniques. We investigate process parameters for the fabrication of sol-gel spin-coated TiO(2) films exhibiting high optical quality comparable with that of ion-beam-sputtered TiO( 2) films. X-ray diffraction studies showed the sol-gel-deposited films to be amorphous for heat treatments below 350 degrees C, whereas the ion-beam-sputtered films were slightly crystalline and exhibited the anatase structure. The refractive index and the extinction coefficient were evaluated from transmittance characteristics in the ultraviolet, visible, and nearinfrared regions. Transmission spectra and ellipsometric measurements showed that spin-coated films were essentially optically equivalent to those prepared by ion-beam sputter deposition.

Analysis of parameter resolution from derivatives of binding isotherms.

Examination of binding information in the form of derivative (or finite difference) measurements is explored (1) experimentally by a thin-layer optical procedure (Dolman, D. & Gill, S. J. (1978) Anal. Biochem. 87, 127-134) and (2) theoretically by simulation in order to determine the influence of the number of data points and their standard error upon the resolvability of binding parameters in cooperative and non-cooperative systems. The data is described by the difference in optical absorbance divided by the change in the logarithm of the ligand activity and each data point is assumed to be influenced by a random error with a given variance. It is found that increasing the number of data points, which in turn effectively reduces the magnitude of the observed absorbance changes, results in an increase in the uncertainty of the resolved parameters of the system. The effect is verified by both experimental and simulation studies. Thus one is led to suggest that fewer measurements for the change of absorbance with larger magnitudes produces the most favorable situation for parameter resolution when the data is in the form of finite difference measurements.

Stabilization of the T-state of hemoglobin.

The effect of inositol hexaphosphate and bezafibrate on binding of O2 and CO to HbAO at high concentrations (1 mM) has been evaluated using thin layer optical techniques. Data analysis shows 1) the occurrence of greatly reduced ligand dependent cooperativity (Hill slope of 2.23 for CO and 1.51 for O2), and 2) the presence of significant triply ligated species. The data fits a nested allosteric two-state MWC model in which the T state consists of two allosteric substrates, Tt and Tr, where Tt binds only to the alpha chains and Tr binds to both alpha and beta chains. The model indicates that the triply ligated species consists of a predominant amount of T form, agreeing with kinetic observations of CO ligated hemoglobin. The maximum amount of triply ligated R molecules (CO or O2) implicated is less than 1%, a result similar to that found previously for binding studies made in the absence of BZF and IHP.

Conformational free energies of myoglobins of small mammals.

Myoglobins from three small placental mammals and one small marsupial were isolated from cardiac or skeletal muscle. The conformational free energies of these four myoglobins were estimated from guanidinium chloride unfolding data at pH 8 and 25 degrees. The myoglobins from rat and rabbit are more stable than that of the most stable myoglobin previously studied, that of the sperm whale. In addition, these two myoglobins unfold with greater cooperativity than previously characterized myoglobins. The data obtained herein demonstrate unequivocally for the first time that the stability of homeotherm myoglobins correlates with neither the size of the organism nor its metabolic rate.