Heterozygotes For Deficiency Research Articles

Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the northern Sardinian experience.

Favism is a potentially fatal manifestation of glucose-6-phosphate dehydrogenase (G6PD) deficiency, and it is therefore a public health problem in areas where this genetic abnormality is common. In the district of Sassari (northern Sardinia), the frequency of G6PD male hemizygotes is approximately 7.5%, and therefore all newborns since 1971 have been screened for G6PD deficiency. We have analyzed the incidence of favism in this community in two 10-year periods: (1) 1961-1970; and (2) 1981-1990. In period 1, there were 508 cases of favism, of which 76% occurred in boys. In period (2) there were 144 cases of favism, of which only 52% in boys. Thus, between the two periods there was an overall decrease in the incidence of favism of 75%, whereas the proportion of girls affected has approximately doubled. These data suggest that neonatal screening and health education programs can produce a substantial decrease in the number of cases of favism, and that the relative increase in favism in girls is possibly due to failure of the screening method used to detect all the heterozygotes for G6PD deficiency.

Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families.

Our primary aim was to determine the extent to which intraplasmic retinyl palmitate (RP) transfers to other lipoprotein particles when chylomicron remnants are not produced and/or the plasma RP residence time is increased. The study was conducted on three familial type I hyperlipoproteinemic patients, four lipoprotein lipase (LpL)-deficient heterozygotes, and three controls on a metabolic research unit. To each subject, a fat load was administered containing 16% of total daily calories in type I patients, 40% in heterozygotes and controls, plus 60,000 U/m2 vitamin A. Triglyceride (TG) and RP levels were evaluated in chylomicron and nonchylomicron fractions. Delay in the clearance of chylomicron fraction RP and the marked deficiency in nonchylomicron-RP (presumed lack of remnant production) in all three type I patients suggests that RP does not demonstrate significant intraplasmic transfer from chylomicrons to existent apolipoprotein B100 particles. In contrast to noncoincident TG and RP peaking in the normal subject, heterozygotes were found to demonstrate coincident plasma TG and RP curves, which is consistent with a common catabolic pathway for both TG and RP and inconsistent with intraplasmic RP transfer. This corroborates reports on compromised chylomicron clearance in heterozygotes. We conclude that RP is an appropriate representative marker for intestinally derived particles in LpL-deficient or partially deficient individuals.

Statistical approaches for the detection of heterozygotes for biotinidase deficiency

We applied and evaluated 3 statistical approaches for the detection of heterozygotes for biotinidase deficiency in a randomly selected population of French adults. The first method, which used a cutoff value to dichotomize the population, lacked sensitivity. The second approach calculated the probability of heterozygosity for a given enzyme activity through the application of Bayes theorem to the normal density functions of the enzyme distributions of the obligate heterozygote and the test populations. A priori values of the means and standard deviations (SDs) of the genotypic distributions were used. This method was sufficiently sensitive for both population screening and genetic counseling, but requires prior knowledge of the frequency of the deficient gene (q). The third approach was similar to the second, however, maximum likelihood estimates of the means and SDs of the genotypic distributions were calculated and used to determine the probability of heterozygosity for a given enzyme activity. This method was as sensitive as the second method and is appropriate for screening populations for which there is little prior information about the gene frequency and the genotypic distributions. This method can also be used to estimate the gene frequency of the disorder within a given ethnic or racial population. Using this method, we estimated the frequency of heterozygotes (2pq) in the French population to be 0.012, which was similar to that estimated from the results of neonatal screening for biotinidase deficiency. These methods can be used to detect heterozygotes and to estimate the gene frequency of other inherited enzyme deficiencies.

Partial Deficiency of α1-Antichymotrypsin Is Associated with Chronic Cryptogenic Liver Disease

alpha 1-Antichymotrypsin (ACT) and alpha 1-antitrypsin (AAT) are two closely related antineutrophil proteinase inhibitors. Whereas AAT deficiency is clearly linked to liver disease, an association between liver disease and partial ACT deficiency has not been established. In a previous study we noted an increased prevalence of liver abnormalities among subjects with heterozygous ACT deficiency. To study a possible association between partial ACT deficiency and liver disease, we screened 316 consecutive patients with biopsy-verified liver disease for partial ACT deficiency and compared the prevalence with that of an unselected adult population in a case-control study. In all, 9 of 316 patients had partial ACT deficiency, which is more than expected (prevalence ratio (PR), 2.46 (1.15-5.27), P less than 0.05). The prevalence of partial ACT deficiency was highest in the chronic active hepatitis (5 of 40; PR, 12.0 (5.33-27.0] and the cryptogenic cirrhosis (3 of 24; PR, 12.0 (4.38-32.9] subgroups. In the chronic active hepatitis subgroup two patients (PR, 8.16 (2.25-29.5] were ACT deficiency heterozygotes, thus partly explaining the high prevalence of partial ACT deficiency among patients with chronic liver disease. The majority (6 of 9) of the patients with partial ACT deficiency lacked autoimmune and viral markers and were thus cryptogenic. The present findings show that partial ACT deficiency and chronic cryptogenic liver disease are associated. To some extent (the true magnitude of which is at present unknown) partial ACT deficiency is caused by a rare trait, heterozygous ACT deficiency, which in parallel with heterozygous alpha 1-antitrypsin deficiency (PiMZ) also seems to be associated with chronic cryptogenic liver disease.

Early signs of vascular disease in homocystinuria: A noninvasive study by ultrasound methods in eight families with cystathionine-β-synthase deficiency

Fourteen patients (six males, eight females; mean age, 20 years) with homocystinuria due to homozygous cystathionine-β-synthase (CBS) deficiency, underwent a vascular examination. Fourteen heterozygotes (seven males, seven females; mean age, 46 years), including 12 parents and one daughter of homozygotes (obligate heterozygotes), and one sister of a homozygote (with low enzyme activity as evaluated in vitro), were also examined. Homozygotes and heterozygotes were compared with two separate control groups of different age (mean age, 20 and 43 years, respectively). Ankle/arm systolic pressure index (by continuous-wave Doppler) was, on average, lower in homozygotes ( P < .01) and heterozygotes ( P < .05) as compared with the controls. An ankle/arm index less than 0.97 and suggesting flow-reducing arterial lesions was found in six (21%) lower limbs of homozygotes versus zero in controls ( P < .05). Echo Doppler (Duplex Scanner) abnormalities, indicating early, non-flow-reducing lesions of iliac arteries were more frequent in homozygotes (seven wall abnormalities or stenoses <15%) than in young controls ( P < .05). The corresponding figures for heterozygotes were seven wall abnormalities or stenoses (1% to 15% and one stenosis 16% to 50%) ( P < .01 v middle-aged controls). Early lesions (three wall abnormalities or stenoses <15%, three stenoses 16% to 50%) were detected in six (23%) internal carotids of heterozygotes versus three (3%) of corresponding controls ( P < .05). Technical limitations precluded the accurate detection of early lesions in the internal carotid arteries of young homozygotes and controls. No significant increase in venous abnormalities (by continuous-wave Doppler) was detected in either group of patients. Early signs of premature arterial disease were thus demonstrated in both homozygotes and heterozygotes for CBS deficiency by highly sensitive, noninvasive, ultrasound methods.

Pairing for recombination in LGV of Caenorhabditis elegans: a model based on recombination in deficiency heterozygotes.

The effect of deficiencies on recombination was studied in Caenorhabditis elegans. Heterozygous deficiencies in the left half of linkage group V [LGV(left)] were shown to inhibit recombination to their right. Fourteen deficiencies, all to the left of unc-46, were analyzed for their effect on recombination along LGV. The deficiencies fell into two groups: 10 "major inhibitors" which reduce recombination to less than 11% of the expected rate between themselves and unc-46; and four "minor inhibitors" which reduce recombination, but to a much lesser extent. All four minor inhibitors delete the left-most known gene on the chromosome, while six of the ten major inhibitors do not (i.e., these are "internal" deficiencies). Where recombination could be measured on both sides of a deficiency, recombination was inhibited to the right but not to the left. In order to explain these results we have erected a model for the manner in which pairing for recombination takes place. In doing so, we identify a new region of LGV, near the left terminus, that is important for the pairing process.

Identification of the Heterozygotes for Deficiency of the β-Subunit of the Eighth Component of Complement by Reduced Levels of C8β and Increased Amounts of Free C8α-γ

Sera from obligate heterozygotes for deficiency of the C8 beta subunit of the eighth component of human complement (C8) were analyzed for the molecular composition of C8. The C8 alpha-gamma and C8 beta subunits were separated by SDS-PAGE, visualized by immunoblotting, and the resulting bands were quantitated by laser densitometry. The laser densitometric absorption data were set to 100 arbitrary units (AU) for both subunits of pooled normal human sera. The AU values of individual normal sera ranged from 45 to 150 AU for C8 alpha-gamma (median 99 AU) and from 45 to 140 AU for C8 beta (median 101), whereas the C8 alpha-gamma/C8 beta-ratio varied from 0.7 to 1.4. Sera from C8 beta-deficient heterozygotes differed, as expected, from the normal sera for the markedly reduced levels of C8 beta (20 to 90 AU, median 55 AU) and for the higher C8 alpha-gamma/C8 beta-ratio (1.3 to 3.5). High voltage agarose gel electrophoresis was used to separate free and C8 beta-bound C8 alpha-gamma. The migration of free and C8 beta-bound C8 alpha-gamma subunit was checked by hemolytic overlay gels and by second dimension SDS-PAGE and immunoblotting. Immunochemical evaluation of C8 alpha-gamma using this system revealed about 5-14% free C8 alpha-gamma in sera with normal C8 and higher levels, from 33-71%, in the C8 beta D heterozygous sera. Functional analysis confirmed the substantial increase of free C8 alpha-gamma in the heterozygous group. We conclude that the C8 in C8 beta D heterozygous sera is characterized by increased amounts of free C8 alpha-gamma due to reduced concentrations of the C8 beta subunit. This finding may help to identify individuals heterozygous for C8 beta deficiency.

Asthma and heterozygous α1‐antichymotrypsin deficiency: a possible association

During studies of families with alpha 1-antichymotrypsin deficiency heterozygotes, an apparently increased prevalence of asthma among first degree relatives was noticed. In a case control study, the prevalence of asthma among first degree relatives of 12 women with heterozygous alpha 1-antichymotrypsin deficiency was compared with that of first degree relatives of 58 matched controls. Secondly, the strength of association between asthma and low or subnormal plasma ACT concentration, in first and second degree relatives to heterozygotes, was assessed. The prevalence of asthma among first degree relatives of women with heterozygous alpha 1-antichymotrypsin deficiency was significantly higher [prevalence ratio 3.22 (1.06-9.83), P = 0.04]. Among heterozygotes, the prevalence of asthma in first and second degree relatives with low plasma alpha 1-antichymotrypsin concentration was higher than in relatives with normal plasma ACT concentration, but the difference in prevalence did not reach statistical significance [prevalence ratio 3.1 (0.96-9.83), P = 0.059]. The findings are in agreement with previous studies and suggest a possible association between asthma and heterozygous alpha 1-antichymotrypsin deficiency.

Macromolecular structure of axon membrane and action potential conduction in myelin deficient and myelin deficient heterozygote rat optic nerves

The macromolecular structure of the axon membrane in optic nerves from 25-day-old male littermate control and myelin deficient (md) rats and 16-month-old md heterozygotic rats was examined with quantitative freeze-fracture electron microscopy. The axon membrane of control optic nerves displayed an asymmetrical partitioning of intramembranous particles (IMPs); P-fracture faces of myelinated internodal axon membrane were more particulate than those of pre-myelinated axons (approximately 1600 v 1100 microns-2, respectively), while relatively few IMPs (approximately 150 microns-2) were present on external faces (E-faces) of internodal or pre-myelinated axon membrane. Amyelinated axons of md optic nerves also exhibited an asymmetrical partitioning of IMPs; protoplasmic membrane face (P-face) IMP densities, taken as a group, exhibited a wide range (approximately 600-2300 microns-2) and, in most regions, E-faces displayed a relatively low IMP density (approximately 175 microns-2). Axons of greater than 0.4 microns diameter exhibited significantly greater mean P-face IMP density than axons less than 0.4 microns diameter. Aggregations of E-face IMPs (approximately 350 microns-2) were occasionally observed along amyelinated axon membrane from md optic nerves. Optic nerves from md heterozygote rats exhibit myelin mosaicism, permitting examination of myelinated and amyelinated axon membrane along the same tract. The axon membrane exhibits different ultrastructure in these two domains. Myelinated internodal axon membrane from md heterozygote optic nerves exhibits similar P- and E-face IMP densities to those of control internodal axolemma (approximately 1800 and 140 microns-2, respectively). Amyelinated axons in the heterozygote exhibit a membrane structure similar to amyelinated axons in md optic nerve. P-face IMP density of large diameter (greater than 0.4 microns) amyelinated axons from md heterozygote optic nerves is significantly greater than that of small calibre (less than 0.4 microns) axons. In most regions, amyelinated axon membrane exhibits a relatively low E-face IMP density (approximately 200 microns-2); however, focal aggregations (approximately 400 microns-2) of E-face particles are present. Electrophysiological recordings demonstrate that amyelinated axons in md optic nerves support the conduction of action potentials. Compound action potentials in md optic nerves exhibit a monophasic configuration, even at 20-days postnatal, similar to that of pre-myelinated optic nerve of 7-day-old normal rats. Moreover, conduction velocities in the amyelinated 20-day-old md optic nerve are similar to those displayed by pre-myelinated axons from 7-day-old optic nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Erythrocyte pyruvate kinase deficiency: a kinetic method for differentiation between heterozygosity and compound-heterozygosity.

The goal of the present study was to search for criteria that allow one to distinguish between normal individuals and heterozygotes as well as compound heterozygotes for pyruvate kinase (PK) deficiency. As the residual activity of PK with heterozygotes was between 35% and 110% of the normal activity, it was necessary to find other methods to prove heterozygosity. The PK in the hemolysates of 23 patients suffering from PK deficiency, 36 paternal and maternal enzymes as well as the enzymes of five heterozygous and four normal siblings together with those of 20 normal individuals, were studied according to the recommendations of the International Committee for Standardization in Haematology. The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up-to-twofold increase of the intracellular concentrations of glucose-6-phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)-binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. The most significant criterium found with all heterozygotes was a mixed cooperativity of the PEP-binding process caused by the presence of a mixture of normal and mutant PK.

The quantitation of biotinidase activity in dried blood spots using microtiter transfer plates: Identification of biotinidase-deficient and heterozygous individuals

A simple and rapid method for the quantitation of biotinidase activity in blood-soaked filter paper spots was developed. The assay measures the release of p-aminobenzoate from N-biotinyl- p-aminobenzoate. A microtiter transfer plate is used to rapidly separate the reaction solution from the filter paper spots. Color is developed and the absorbance is determined using a microplate reader. The biotinidase activity in frozen filter spots correlates well with the activity in serum ( r = 0.94). The enzyme activities of obligate heterozygotes for biotinidase deficiency were significantly different from those with normal activity ( P = 0.03). This rapid screening procedure can be used to quantitate biotinidase activity in newborn screening samples, identify heterozygotes, and estimate the gene frequency and incidence of biotinidase deficiency in large populations. In addition, the use of microtiter transfer plates can be applied to other assays in which the separation of the incubation solution from a filter paper spot is required.

The relationship between CR3 deficiency and neutrophil actin assembly

Polymorphonuclear leukocytes (PMN) with a deficiency of the complement receptor type 3 (CR3) membrane glycoprotein family have impairments in the ability to adhere to surfaces as well as chemotactic and phagocytic defects, processes that require a functional contractile apparatus. PMN from the patient with neutrophil actin dysfunction (NAD) displayed similar functional characteristics to those with CR3 deficiency suggesting the two disorders may be the same disease. In order to evaluate the relationship between CR3 deficiency and actin assembly, actin filament assembly was measured in PMN from six previously reported homozygotes (two severe and four moderate CR3-deficient patients) as well as five heterozygotes for CR3 deficiency. PMN from all patients had normal unstimulated concentrations of F-actin and after exposure to the chemotactic peptide FMLP (5 x 10(-7) mol/L for 5 to 40 seconds at 25 degrees C) assembled actin normally. Pretreatment of normal PMN with concentrations of monoclonal anti-alpha CR3 antibody, capable of blocking PMN adherence, also failed to impair FMLP- induced actin filament assembly. CR3 glycoprotein expression was measured in PMNs from the mother, father, and older sister of the NAD patient (N Engl J Med 291:1093, 1974). Actin filament assembly was recently shown to be defective in PMNs from all three family members. The total concentrations of the alpha and beta CR3 subunits were below normal in PMN detergent extracts from the mother (25% of simultaneous controls) and older sister (56% of control). PMN surface expression of these two subunits was also found to be depressed (mother, 50%; older sister, 63% of control). These findings suggest these two NAD family members are heterozygote carriers for CR3 deficiency as well as NAD. Simultaneous studies of the father, however, demonstrated normal total concentrations of both the alpha and beta CR3 subunits (126% of controls) as well as normal surface expression of both subunits after phorbol myristate acetate stimulation and incubation at 37 degrees C (mean, 112% of controls) but slightly lower than normal levels after FMLP stimulation (mean, 83%). These findings indicate that CR3 deficiency generally is not associated with defective actin filament assembly and support the conclusion that NAD represents a unique kindred in which PMN actin function differs from previously reported genotypes of CR3 deficiency.

The Relationship Between CR3 Deficiency and Neutrophil Actin Assembly

Polymorphonuclear leukocytes (PMN) with a deficiency of the complement receptor type 3 (CR3) membrane glycoprotein family have impairments in the ability to adhere to surfaces as well as chemotactic and phagocytic defects, processes that require a functional contractile apparatus. PMN from the patient with neutrophil actin dysfunction (NAD) displayed similar functional characteristics to those with CR3 deficiency suggesting the two disorders may be the same disease. In order to evaluate the relationship between CR3 deficiency and actin assembly, actin filament assembly was measured in PMN from six previously reported homozygotes (two severe and four moderate CR3-deficient patients) as well as five heterozygotes for CR3 deficiency. PMN from all patients had normal unstimulated concentrations of F-actin and after exposure to the chemotactic peptide FMLP (5 x 10(-7) mol/L for 5 to 40 seconds at 25 degrees C) assembled actin normally. Pretreatment of normal PMN with concentrations of monoclonal anti-alpha CR3 antibody, capable of blocking PMN adherence, also failed to impair FMLP-induced actin filament assembly. CR3 glycoprotein expression was measured in PMNs from the mother, father, and older sister of the NAD patient (N Engl J Med 291:1093, 1974). Actin filament assembly was recently shown to be defective in PMNs from all three family members. The total concentrations of the alpha and beta CR3 subunits were below normal in PMN detergent extracts from the mother (25% of simultaneous controls) and older sister (56% of control). PMN surface expression of these two subunits was also found to be depressed (mother, 50%; older sister, 63% of control). These findings suggest these two NAD family members are heterozygote carriers for CR3 deficiency as well as NAD. Simultaneous studies of the father, however, demonstrated normal total concentrations of both the alpha and beta CR3 subunits (126% of controls) as well as normal surface expression of both subunits after phorbol myristate acetate stimulation and incubation at 37 degrees C (mean, 112% of controls) but slightly lower than normal levels after FMLP stimulation (mean, 83%). These findings indicate that CR3 deficiency generally is not associated with defective actin filament assembly and support the conclusion that NAD represents a unique kindred in which PMN actin function differs from previously reported genotypes of CR3 deficiency.

Detection and characterization of the heterozygote state for lipoprotein lipase deficiency.

Because there are no characteristic clinical or biochemical manifestations, the heterozygote state for lipoprotein lipase (LPL) deficiency has been difficult to detect. Measurements of postheparin plasma LPL activity and of LPL mass were performed in six families of probands with LPL deficiency to characterize the heterozygote state. LPL mass was measured in a sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (5D2) that had been produced against bovine milk LPL. Thirteen obligate heterozygotes from these families had reduced LPL activity and mass below the 95th percent confidence limits of 34 normal controls, while one obligate heterozygote had LPL activity and mass between the 90th and 95th percent confidence limits. Potential heterozygotes in these families were identified as normal (n = 8) or heterozygotes (n = 6) by comparison to the 95th percent confidence limits of the controls. Some relatives in four of the six families exhibited mild hyperlipidemia, similar to the pattern seen in familial combined hyperlipidemia (FCHL). The hyperlipidemia segregated with the heterozygote state for LPL deficiency in these families (p less than 0.03). High density lipoprotein (HDL) cholesterol was significantly reduced in the heterozygotes for LPL deficiency (p less than 0.01). The measurement of LPL activity and mass allows identification of the heterozygote state for LPL deficiency, which is characterized by variable expressions of hyperlipidemia and reduced HDL cholesterol. These results suggest that the heterozygote state for LPL deficiency may form one subset of FCHL.

Interaction of the Stubble-stubbloid locus and the Broad-complex of Drosophila melanogaster.

The 2B5 region on the X chromosome of Drosophila melanogaster forms an early ecdysone puff at the end of the third instar. The region is coextensive with a complex genetic locus, the Broad-Complex (BR-C). The BR-C is a regulatory gene that contains two major functional domains, the br domain and the l(1)2Bc domain. BR-C mutants prevent metamorphosis, including morphogenesis of imaginal discs; br mutants prevent elongation and eversion of appendages and l(1)2Bc mutants prevent fusion of the discs. The Stubble-stubbloid (Sb-sbd) locus at 89B9-10 is best known for the effects of its mutants on bristle structure. Mutants of the BR-C and the Sb-sbd locus interact to produce severe malformation of appendages. Viable heteroallelic and homoallelic combinations of Sb-sbd mutants, including loss-of-function mutants, affect the elongation of imaginal disc appendages. Thus, the Sb-sbd+ product is essential for normal appendage elongation. Sb-sbd mutants, however, do not affect eversion or fusion of discs. Correspondingly, only BR-C mutants deficient in br function interact with Sb-sbd mutants. The interaction occurs in deficiency heterozygotes using single, wild-type doses of the BR-C, of the Sb-sbd locus, or of both loci. These last results are formally consistent with the possibility that the BR-C acts as a positive regulator of the Sb-sbd locus. The data do not exclude other possible nonregulatory interactions between the two loci, e.g., interactions between the products of both genes.

Screening heterozygotes for 21-hydroxylase deficiency among hirsute women: lack of utility of the adrenocorticotropin hormone test

Heterozygosity for 21-hydroxylase deficiency (21-OHD) was investigated in 174 adult hirsute women by using the sum of the incremental responses of serum 17 alpha-hydroxyprogesterone (17 alpha-OHP) and progesterone (P) (delta 17 alpha-OHP + P), 60 minutes after a 0.25 mg intravenous (IV) bolus of synthetic adrenocorticotropic hormone (ACTH). The distribution of 17 alpha-OHP + P in hirsute women was bimodal, allowing two subgroups to be distinguished. In one subgroup including 137 patients, the mode was similar to controls and all values were lower than 3 ng/ml. Thirty-seven (21%) patients constituted another subgroup with values higher than 3 ng/ml and could a priori have been considered as heterozygotes for 21-OHD. However, human leukocyte antigen genotyping provided no conclusive evidence that this subgroup included exclusively heterozygotes for the 21-OHD.

Erythrocyte pyrimidine 5'-nucleotidase and deoxynucleotidase isozymes: metallosensitivity and kinetics.

Erythrocytes from a subject with classical pyrimidine 5'-nucleotidase (P5N) deficiency (PND) possessed typically low nucleotidase activity with uridine 5'-monophosphate (UMP) and cytidine 5'-monophosphate (CMP) as the substrates with subnormal dephosphorylation of 2'-deoxy thymidine 5'-monophosphate (dTMP) and 2'-deoxyuridine 5'-monophosphate (dUMP) and intermediate activity with 2'-deoxycytidine 5'-monophosphate (dCMP). Contrary to previously reported data, there was enzyme activity with all five substrates. The metallosensitivities of the P5N isozymes using UMP, dUMP, dCMP and dTMP as the substrates were defined. Nucleotidase (P5N) is slightly more sensitive than 2'-deoxy-pyrimidine 5'-nucleotidase (dP5N) to inhibition by lead, copper and mercury. Chromium stimulated more enzyme activity with dCMP than other substrates. Apparent Michaelis constants (Km) were calculated for UMP, CMP, dUMP, dCMP, and dTMP for PND and control subjects. Optimal activity was at pH 7.0-7.8 when using UMP and CMP as the substrates but at pH 5.5-6.5 with dUMP, dCMP and dTMP as the substrates. The Km, pH optima and metallosensitivities were, however, consistent with electrophoretic evidence for two and probably three isozymes: P5N with maximal affinity for UMP and CMP; dP5N with maximal affinity for dUMP and dTMP; and a closely related dCMPase. The relative activity with representative substrates can be used to distinguish homozygotes and heterozygotes for P5N deficiency and subjects with heavy metal exposure.

Study of Hepatic Fructose Metabolism in Heterozygotes for Aldolase-B Deficiency by 31-Phosphorus Magnetic Resonance Spectroscopy (31-P MRS)

Conference Abstract| December 01 1987 Study of Hepatic Fructose Metabolism in Heterozygotes for Aldolase-B Deficiency by 31-Phosphorus Magnetic Resonance Spectroscopy (31-P MRS) R. Oberhansli; R. Oberhansli 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar B. Rajagopalan; B. Rajagopalan 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar D. Taylor; D. Taylor 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar G.K. Radda; G.K. Radda 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar J. Collins; J. Collins 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar J.V. Leonard; J.V. Leonard 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar N. Herschcovitz; N. Herschcovitz 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar H. Schwartz H. Schwartz 1Nuffield Department of Clinical Medicine, and MRC Clinical Magnetic Resonance Laboratory, University of Oxford, Institute of Chila Health, London and Innel Hospital, Berne, Switzerland Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1987) 73 (s17): 56P. https://doi.org/10.1042/cs073056P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation R. Oberhansli, B. Rajagopalan, D. Taylor, G.K. Radda, J. Collins, J.V. Leonard, N. Herschcovitz, H. Schwartz; Study of Hepatic Fructose Metabolism in Heterozygotes for Aldolase-B Deficiency by 31-Phosphorus Magnetic Resonance Spectroscopy (31-P MRS). Clin Sci (Lond) 1 December 1987; 73 (s17): 56P. doi: https://doi.org/10.1042/cs073056P Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. Article PDF first page preview Close Modal You do not currently have access to this content.

Evaluation of the nature of mildly prolonged prothrombin times.

Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time (greater than 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (mean 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (mean 45.5 U/dl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII+) and the nondiscrepant one (VII-/R). Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi. We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since the other vitamin K-dependent clotting factors were normal; the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and F VII:C and F VII:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency. On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency. In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.

Early Identification of chlorophyil deficiency heterozygotes in large-seeded legumes

Early Identification of chlorophyil deficiency heterozygotes in large-seeded legumes