Regional mapping of the locus for hexokinase-1 (HK1) to 10p11 equals to q23 by gene dosage in human fibroblasts.
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Animals↗
Biomedical subjects
N E Simpson
Publications and source records attributed to N E Simpson.
Exclusion of linkage between the loci for multiple endocrine neoplasia type-2 (MEN-2) and HLA.
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Chromosome Mapping↗
Strongyloides ratti: studies of 75Se-labelled larvae of the homogonic strain in female hosts.
A prediction of the hypothesis of Wilson (1977, 1980 a, b) to account for larval migration of homogonic Strongyloides ratti in the host is that the pattern of invasion of the mammary gland of a lactating rat will be quantitatively similar on both sides and independent of the point of entry into the body. Twenty-one suckled mother rats in 6 experiments in which live 75Se-labelled 3rd-stage homogonic larvae were injected under the skin of the upper flank had an overall distribution of label 30 h post-injection, as a percentage of the initial dose, in the quadrants, I (rear, injection side, II (rear, opposite injection side), III (front, injection side) and IV (front, opposite injection side) of the mammary gland as follows: 27.4%, 1.27%, 1.98% and 1.24%. Quantitative changes in mammary label between 30 and 48 h post-injection using live larvae, differences between mothers and virgins, and results after injection of heat-killed labelled larvae, confirm that the pattern is representative of the behaviour of normal (unlabelled) worms when injected. The theory is therefore disproved. The findings are put forward as the first quantitative evidence for major lymphatic involvement in migration of a skin-penetrating roundworm. They need confirmation in similar experiments in which worms are allowed to penetrate the skin naturally. The role of isotope-labelled larvae versus traditional methods of estimating parasite content of host tissue is discussed.
Animals↗
Strongyloides ratti (homogonic): the time-course of early migration in the generalized host deduced from experiments in lactating rats.
Unsuckled mother rats given a 1 h suckling stimulus 3 h after subcutaneous injection of an exact dose of homogonic Strongyloides ratti allow fewer worms to develop in their intestines by day 9 than nulliparous rats (Wilson & Simpson, 1981). This effect is studied in more detail in terms of the length of time between weaning and stimulus (W leads to S) and injection and stimulus (I leads to S). It was observable with a W leads to S of 30 h but this and a period of 5 h were less effective than 24 h. With W leads to S constant at 24 h, significantly more worms developed in mothers when I leads to S was 24 h compared to 3 h and 10 h (P less than 0.005). The data, combined with those from nulliparous controls, are presented as a measure of the change with time of numbers of larvae in that compartment of the system which gives access to the stimulated mammary gland. It is argued that the particular compartment is the local lymph node draining the injection site and that the kinetics deduced are applicable to migration in the rat in general.
Animals↗
Multiple endocrine neoplasia, type II: a combined surgical and genetic approach to treatment.
A family with multiple endocrine neoplasia, type II living in southeastern Ontario is described. Twenty individuals are known to have had medullary carcinoma of the thyroid, pheochromocytoma or both, the diagnosis of multiple endocrine neoplasia. type II is strongly suspected in five other individuals in the earlier generations. In this family the diseases seems to be transmitted by an autosomal dominant gene. A screening program set up for the family in 1977 has in 2 years identified four asymptomatic individuals (three with medullary carcinoma of the thyroid and one with this carcinoma and a pheochromocytoma). The family background, clinical picture, treatment and some of the problems of the screening program are described.
Adolescent↗
Familial cutaneous amyloidosis with systemic manifestations in males.
We describe a family in which two males and seven females have brown pigmentation of the skin. In the females, the type and distribution of the pigmentation mimicked incontinentia pigmenti; in the males, the pattern was reticulate. The histological appearance was the same in both sexes with amyloid deposits in the papillary dermis, melanin in the basal layer, and slight hyperkeratosis. The females were otherwise normal. Both males had thrived poorly as infants but had survived. One had severe gastroenteritis with blood in the stools starting at the age of three weeks followed by seizures, hemiplegia, and developmental delay; the other had recurrent pneumonia throughout life, a urethral stricture, inguinal herniae, and near-blindness from amyloid deposition in the cornea. Five other males in the family had had severe illnesses. Two died of pneumonia by three months. One died at three months from colitis. Both remaining boys had colitis as infants, failed to thrive, and developed recurrent pneumonia from which one died at three years. We think all of these relatives had the same disease carried by a single gene with pleiotropic effects. The most likely form of inheritance is X-linked.
Adolescent↗
Cholinesterase Newfoundland: a new succinylcholine-sensitive variant of cholinesterase at locus 1.
A family from Newfoundland was found to have a new rare variant for plasma cholinesterase (E.C.3.1.1.8) recognized by a high-percentage inhibition by dibucaine (DN), particularly when succinyldithiocholine was used as substrate (DNSDTC) but also somewhat high when benzoylcholine was substrate (DNBZCH). The family data demonstrated that the variant is determined by an allele of the usual and atypical alleles at locus 1, and the new allele is designated CHE1*NFLD. The proband who was heterozygous for the Newfoundland and atypical alleles had shown sensitivity to succinylcholine. It is postulated that cholinesterase Newfoundland (NFLD) has a reduced affinity for succinylcholine. Samples selected for high DNs with a benzoylcholine from 200 Canadian Caucasians and 70 Newfoundlanders did not have the variant, and, therefore, it is assumed that the remainder of the samples did not have the variant.
Adult↗
Dic(21;21) in a Down's syndrome child with an unusual chromosome 9 variant in the mother.
A child with characteristic clinical features of Down's syndrome and raised red cell SOD-1 activity was found to have, in addition to a single chromosome 21, a reverse dicentric tandem translocation of two No 21s with dual NORs and C band regions. The breakpoints on the chromosomes involved in the translocation were at the most distal end of the long arms (21q223). The phenotypically normal mother carried a rare variant of a chromosome 9.
Adult↗
The genetics of diabetes mellitus in man.
The genetics of diabetes mellitus in man has been reviewed. The evidence for genetic heterogeneity on clinical, biochemical and HLA (histocompatibility leukocyte antigens) data is presented. An attempt is made to interpret the meaning of the associations of the disease and certain HLA antigens and the complement factor, properdin in populations and in families. The population data can be best explained by the linkage disequilibrium hypothesis requiring tight linkage between the DS (diabetes susceptibility) locus and those in the MHC (major histocompatibility complex). Linkage between the DS locus and MHC from family data is estimated to be about 14%, which is not likely tight enough to be compatible with the population data; and a one locus or one allele hypothesis and genetic heterogeneity is postulated as the best explanation of the incompatibility between population and family data. It is still impossible to precisely define the exact genetic hypothesis for diabetes in man.
Alleles↗
Antenatal diagnosis of neural tube defects in Canada: extension of a collaborative study.
Experience with the diagnosis of neural tube defects from alpha1-fetoprotein (AFP) concentrations in amniotic fluid is reported from a prospective study of five laboratories testing for 13 Canadian genetic centres. The results of the study indicate that antenatal diagnosis of open neural tube defects is being carried out effectively in Canada (in 99.2% of cases the AFP measurements were interpreted correctly). Amniocentesis should be recommended to women at high risk for having a child with a neural tube defect (i.e., those who have a child, a parent or a sibling with a neural tube defect). The rate of neural tube defects in 182 high-risk pregnancies was 2.2% for an open defect and 1.1% for a closed defect, whereas the rate in 673 pregnancies in which amniocentesis was being performed for other reasons was 0.3%. This suggests that the AFP concentration should be measured in any sample of amniotic fluid collected for other reasons (usually fetal karyotyping). There were three instances of false-negative results, for a rate of 0.4%. Two closed neural tube defects were not detected; this limitation of the test has also been found by others. One of the six fetuses with an open neural tube defect, who died in utero, had a large myelocele in the neck that was not recognized. There were also four instances of false-positive results, for a rate of 0.5%. The findings suggest that AFP values that are more than 2 but less than 7 standard deviations (SDs) above the mean may indicate a neural tube defect, and that values 7 or more SDs above the mean very likely indicate such a defect, although other reasons for such high values (e.g., fetal erythrocytes in the amniotic fluid, intrauterine death and mistaken gestational age) must be ruled out by other methods.
Amniocentesis↗
Cat primary canal neurons: relation of conduction velocity to resting and dynamic firing characteristics.
Spontaneous discharge patterns of first-order canal afferents were analyzed in cats anethetized with pentobarbital sodium with particular emphasis on the relationship of regularity of resting discharge, sensitivity to angular acceleration and adaptation to the time delay between electrical labyrinthine stimulation and recording from afferents near Scarpa's ganglion. Regular units were found to have a high resting rate, low sensitivity to angular acceleration, were mostly nonadapting during prolonged acceleration and showed relatively long latency to electrical stimulation. Irregular units tended to have a low resting rate, high sensitivity, frequently showed adaptation and had short latencies. Intermediate neurons had mixed characteristics of regular and irregular units. In medulated nerve fibers, a direct relation exists between conduction velocity and fiber diameter. As latency is due primarily to conduction in the first-order axon, we may speculate that regular neurons have thin fibers which innervate the slope of the crista, irregular neurons have thick fibers which innervate the summit, and intermediate units have medium caliber fibers which innervate both the slope and summit of the crista ampullaris.
Animals↗
Confirmation of regional assignment of nucleoside phosphorylase (NP) on chromosome 14 by gene dosage studies.
Gene dosage studies yielded results consistent with assignment of the locus for nucleoside phosphorylase to band 14q13. The red blood cells from a patient with the karyotype 47,XX,+der(14),t(8;14)(8qter leads to 8q24::14q21 leads to 14pter)pat had enzyme activity 50% higher than red cells from 47 normal controls, two trisomies involving chromosomes other than 14, and five balanced translocations involving chromosome 14. On the other hand, the red cells of a case with a karyotype 45,XX,-14,-22+der(22),t(14;22)(14qter leads to 14q11 or 14q12::22p11 leads to 22qter)mat and a case with a a karyotype 47,XX,+der(14),t(14;16)(14pter leads to 14q11::16q24 leads to 16qter)mat had normal activity
Child, Preschool↗
Hereditary angioneurotic edema and Charcot-Marie-Tooth disease in the same family.
In one family two genetic diseases were transmitted as autosomal dominant traits; hereditary angioneurotic edema was inherited from the paternal side and Charcot-Marie Tooth disease from the maternal side of the family. The conditions occurred separately in 8 and 11 members respectively and together (an exceedingly rare occurrence) in 3. Of six siblings, two girls and four boys, all had Charcot-Marie-Tooth disease, and three, the two girls and one of the boys, also had hereditary angioneurotic edema.
Adolescent↗
Group-specific component, alpha1-antitrypsin and esterase D in Canadian Eskimos.
Three genetic markers - group-specific component (Gc), alpha1-antitrypsin, and esterase D - were examined in a population of Eskimos from Igloolik in the eastern Canadian Arctic. Gc and esterase D were found to be polymorphic. In addition to the common Gc types, an anodal variant called Gc Igloolik was found, probably identical to previously reported Gc Eskimo. Gene frequencies were Gc1: 0.6524, Gc2: 0.3373, GcIgl: 0.0104, for 338 Eskimos. Genetic types of alpha1-antitrypsin (Pi types) were mostly M, with two MS sibs who were half Caucasian, in 170 Eskimos. Frequencies of the esterase D allele in 336 Eskimos were EsD1: 0.7083, EsD2: 0.2917. The frequencies of Gc2 and EsD2 are both higher than are found in Caucasian populations.
Canada↗
Familial translocation t(8;14) with a case of tertiary trisomy, +14q-.
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Chromosome Banding↗
The relationship of conduction velocity to other physiological properties of the cat's horizontal canal neurons.
The conduction velocity and other physiological characteristics of the first order horizontal canal afferents were studied in 24 anesthesized cats. From their spontaneous discharge patterns, neurons were classified into three groups: regular, intermediate and irregular; The irregular units tended to have a low resting rate, high sensitivity to angular acceleration, frequently exhibited adaptation during prolonged acceleration, and showed a short latency from the time of electric stimulation of the labyrinth to recording the action potential near Scarpa's ganglion. The regular units tended to have a high resting discharge rate, low sensitivity, were mostly non-adapting, and showed longer latency to electric stimulation. The intermediate neurons had a mixed character of regular and irregular units. Based on the very short conduction times (mean 0.34 msec) and the work of Moxon (1971), we conclude the locus of activation of electrical stimulation is neural rather than the receptor cells. Since the latency is due predominantly to conduction in the first order axon, and since there is a direct linear relation between conduction velocity and fiber diameter in the medullated nerve fibers, it is possible to speculate that the regular cells have thin fibers which innervate the slope of the crista, the irregular neurons have thick fibers which innervate the summit of the crista, and the intermediate units have medium caliber fibers which innervate both the slope and summit of the crista ampullaris.
Action Potentials↗
Ocular accomodative changes in humans induced by positional changes with respect to gravity.
Ocular accomodation was measured in human subjects while they were rotated at 1 degree/sec about their naso-occipital axes. Sixteen normal subjects were tested with 45 complete and 27 partial revolutions. Naso-occipital rotations ipsilateral to the eye being observed caused accommodative, lens-thickening changes. This effect begin at about 14 degrees from head upright position, tended to reach a maximum by 45 degrees and usually stayed at this level until about 90 degrees. The values tended to return to control level by 180 degrees. With naso-occipital roll in the direction opposite to the eye being observed, there was little change until about 135 degrees at which point further roll was typically clear accomodation. This continued to a maximum at about 270 degrees rotation, and at about 350 degrees returned to control values. Arguments are presented relating this response to the utricles, which are approximately parallel to earth horizontal. The threshold of this response, between 3.7 and 77 cm/sec2, is similar to the threshold of linear acceleration when measured by other means.
Accommodation, Ocular↗
Prenatal diagnosis of genetic disease in Canada: report of a collaborative study.
A study of 1223 amniocenteses carried out during 1020 pregnancies in 990 women showed that 2nd-trimester amniocentesis at about 16 weeks' gestation is a safe, accurate and reliable procedure for the diagnosis of certain classes of genetic disease when it is monitored by ultrasound, performed by a trained obstetrician and carried out in a major health sciences centre. The percentage of fetal losses (4.7%) and neonatal deaths (0.5%) during the study was not greater than in control samples for women 35 years of age and older. The best results were obtained when needles of gauge 20 or 21 were used. The use of needles of gauge 19 or larger and more than two insertions during a single amniocentesis were associated with a significantly greater frequency of fetal loss than a second or even a third amniocentesis during the same pregnancy. For 39 fetuses (3.8%) a diagnosis of a genetic abnormality was made and 23 male fetuses were found to be potentially hemizygous for an X-linked gene. There were 51 therapeutic abortions as a result of the diagnosis. Sixty-six tests (5.4%) gave an inconclusive result and seven (0.6%) gave an erroneous diagnosis; five of the latter (two false-positives and three false-negatives) resulted from the alpha1-fetoprotein test for neural-tube defects and in two cases the sex was incorrectly determined. The frequency of all chromosome abnormalities was 1:20 when the mother's age was 40 years or more and 1:60 when the mother's age was between 35 and 39 years. When a mother had previously had a child with a chromosome abnormality the risk of recurrence of such an abnormality was 1:100 when the age of the mother was 35 years or more.
Abortion, Therapeutic↗