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Biomedical subjects

J V Neel

Publications and source records attributed to J V Neel.

At least 109 records · Page 6Linked to original sources
PubMed1985

Inherited thermostability variants of seven enzymes in a Japanese population.

The frequency of inherited variations in thermostability was investigated in a series of seven enzymes in a Japanese population. Among a total of 5930 determinations, nine variants were encountered. In each instance one parent exhibited a similar finding. It is suggested that this procedure should detect a high proportion of the variants of these enzymes characterized by amino acid substitutions not altering molecular charge. Failure to detect more such thermostability variants is interpreted to mean that electrophoresis not only detects amino acid substitutions altering molecular charge but also a considerable proportion of those that do not alter charge.

Adenylate Kinase↗
PubMed1985

Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians.

Yanomama Indians from the jungles of southern Venezuela and northern Brazil excreted 1 +/- 1.5 mEq of Na and 203 +/- 109 mEq of K and had low blood pressure (BP), 102/62 mm Hg). In comparison, Guaymi Indians of Panama excreted 103 +/- 50 mEq of Na and 118 +/- 52 mEq of K and had significantly higher BP (114/75 mm Hg, p less than 0.001). Elucidating the renin-aldosterone axis, total upright serum aldosterone in 34 Yanomama was high (85.6 +/- 78 ng/100 ml). The binding capacities of thermolabile (ABG) and thermostable (ABG-Ts) serum globulins for aldosterone were elevated at 23.8 +/- 6 and 14.9 +/- 2.6%, respectively; consequently, total ABG- plus ABG-Ts- bound aldosterone was as high as 38.6 +/- 6.3%. Plasma renin activity (PRA 10.3 +/- 2.4 ng/ml/h) and urinary aldosterone 18-glucuronide (70.3 +/- 30 micrograms/24 h) in 17 Yanomama were also very high. In contrast, total serum corticosteroids and corticosteroid-binding globulin (CBG) binding capacity were normal, suggesting normal ACTH activity. PRA correlated positively with total (r = 0.47, p less than 0.05) and free (r = 0.47, p less than 0.05) serum aldosterone, which in turn showed a negative trend with Na (r = 0.33, NS) excretion. The effect of high dietary K appeared less important to aldosterone stimulation and PRA suppression. ABG-bound aldosterone (r = 0.43, p less than 0.01) as well as ABG-Ts (r = 0.56, p less than 0.05) were negatively correlated with diastolic but not systolic BP. The total ABG- and ABG-Ts-bound fraction correlated with diastolic BP (r = 0.43, p less than 0.05) in contrast to the free fraction (r = 0.08, NS) or total aldosterone (r = -0.09). Apparently, only bound serum aldosterone is important for the maintenance of diastolic BP. High serum aldosterone, with elevated excretion, indicates an increased secretion rate; increased serum protein binding suggests an increased tissular activity and alterations in aldosterone metabolism. In Guaymi Indians both total plasma aldosterone (14.5 +/- 65 ng/100 ml) and urinary aldosterone (8.1 +/- 4.8 micrograms/creatinine excretion) were normal. ABG-binding capacity for aldosterone was moderately elevated (17.8 +/- 4.8) and of ABG-Ts normal (10.2 +/- 1.2) suggesting a nearly normal aldosterone metabolism and regulation. The BP of Guaymi was significantly higher than that of the Yanomama.

Adolescent↗
PubMed1984

Failure to demonstrate mutations affecting protein structure or function in children with congenital defects or born prematurely.

An effort has been made to confirm the report [Dubinin, N. P. & Altukhov, Y. P. (1979) Proc. Natl. Acad. Sci. USA 76, 5226-5229] that children born prematurely or exhibiting congenital defects can be shown to exhibit relatively high frequencies of rare (nonpolymorphic) electrophoretic variants of proteins and that a large proportion of these variants are due to mutation in either the father or the mother. In a series of 178 children who were comparable with those described in the earlier report, we failed to encounter a high frequency of these variants in some 5341 determinations involving 45 proteins, nor were any mutations observed. Data from 1583 determinations of enzyme activity on a subset of the panel of proteins were also unremarkable. We are thus unable to confirm the earlier report.

Blood Proteins↗
PubMed1984

Identification of genetic variants in erythrocyte lysate by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis followed by silver-staining has been employed to study 27 red cell lysates for genetic variation. Forty-six polypeptides selected without respect to variability were considered suitable for scoring. Only 23 of the total of 1,242 polypeptides could not be scored unambiguously. Of the remaining 1,219 polypeptides, 38 exhibited the combination of a normal and a variant polypeptide. All variants were present in either the father or the mother of the subjects. The observed index of heterozygosity was 3.1% +/- 0.5%.

Adult↗
PubMed1984

Bilirubin binding by variant albumins in Yanomama Indians.

Sera of Yanomama Indians homozygous for the common albumin allele exhibited greater total effective-binding capacities for bilirubin than did sera of individuals homozygous for the Yan-2 albumin variant in the in vitro experiments described herein. Total effective binding capacities of heterozygous samples were close to those of homozygotes for AlA. Individuals homozygous for Yan-2 might experience a higher risk of bilirubin toxicity and related disorders during the neonatal period. Further studies of binding and displacement of bilirubin by competitors, such as dietary or medicinal coumarins, might help explain the existence of these polymorphisms and the significance of phenotypic differences in binding to bilirubin.

Alleles↗
PubMed1984

A "disproportion" between the frequency of rare electropmorphs and enzyme deficiency variants in Amerindians.

Our previous studies have revealed a higher frequency of nonpolymorphic electrophoretic variants in blood samples from Amerindians than in similar samples from Caucasians and Japanese. Our present study finds, by contrast, that the frequency of deficiency variants of 11 erythrocyte enzymes, sampled in nine Amerindian tribes of Central and South America, is essentially the same (1.5/1,000 determinations) as in Caucasians or Japanese. Possible explanations of the elevated frequency of mobility variants in the tropical-zone/ unacculturated populations include: higher mutation rates resulting in both electrophoretic and activity variants in Amerindians but increased selection against deficiency variants in the Amerindians, or comparable mutation rates in both populations coupled with a greater probability of a mobility variant attaining a relatively high frequency among the Amerindians.

Electrophoresis↗
PubMed1983

Two-dimensional electrophoresis of plasma polypeptides reveals "high" heterozygosity indices.

A series of 62 plasma samples have been examined for genetic variation by the technique of two-dimensional polyacrylamide gel electrophoresis followed by silver-staining of the gels. Twenty polypeptides chosen without respect to variability were considered suitable for scoring. Of the total of 1,240 polypeptides, 29 could not be scored unambiguously. Seventy-five of the remaining 1,211 exhibited the combination of a normal and a variant polypeptide. All variants were present in either the father or the mother of the subject. This index of heterozygosity (6.2 +/- 0.7%) is substantially higher than those reported by others in similar studies of human fibroblasts, lymphocytes, kidney, or brain cells.

Blood Proteins↗
PubMed1983

Multiple-locus departures from panmictic equilibrium within and between village gene pools of Amerindian tribes at different stages of agglomeration.

A comparative analysis of departures from multiple-locus Hardy-Weinberg equilibrium is presented for a set of four tribal Indian groups (the Yanomama, Makiritare, Wapishana and Ticuna) from the lowlands of South America. These tribes span a range of agglomeration and acculturation from the most traditional, swidden horticulturalists to frontier townspeople. The small-group social organization typical of traditional horticulturalists leads to substantial departures from tribal panmixia, as manifested by the distribution of multiple-locus genotypes both within and between villages. Within villages, the departures from single-locus Hardy-Weinberg equilibrium are small and nonsignificant, but the departures from gametic equilibrium (independence of loci) are substantial, even for the unlinked loci we have used to characterize these populations. The departures from single-locus homogeneity across villages are also substantial. One of the normal concomitants of increasing acculturation in this setting is an increase in agglomeration. As agglomeration increases, the departures from multiple-locus panmixia decrease, a process that can be very rapid. We discuss both the shifting balance theory of evolution and punctuated evolutionary rates in light of the small group social organization that must have obtained throughout most of human evolution.

Brazil↗
PubMed1983

The frequency among Japanese of heterozygotes for deficiency variants of 11 enzymes.

Eleven human enzymes, chosen for this study because of relatively small coefficients of variation for mean activity, have been surveyed for the frequency with which activities less than or equal to 66% of the mean value occur. This criterion should detect almost all heterozygotes for variants lacking any activity plus a fraction of the persons with variants characterized by markedly depressed activity and/or instability. The enzymes surveyed are TPI, PGK, AK1, LDH, GAPD, GPI, PK, 6PGD, G6PD, GOT1, and HK. The number of determinations per enzyme ranged from 310 to 3,173, for a total of 26,634 determinations. Family studies have thus far been possible in 52 instances in which the initial observation of activity less than or equal to 66% of normal was confirmed. In every instance, a parent exhibited a similar finding, giving confidence that a true genetic entity was being detected. With this approach, the frequency of heterozygotes per 1,000 determinations varied from 0.0 (AK1, 6PGD) to 13.8 (PK), with an average of 2.4. For these same systems, in this laboratory the frequency of "rare" electrophoretic variants is 2.3/1,000, the ratio of the latter to the former thus being 1.0 in Japanese. Our experience with these deficiency phenotypes to date suggests that for selected enzymes such phenotypes can be incorporated into a program designed to detect mutational events.

Enzymes↗
PubMed1982

Dermatoglyphic characters and physique: a correlation study.

The association of anthropometrics, particularly hand measurements, with dermatoglyphic characters is quantified. Children with square hands exhibit higher main line indices, a-b ridge counts, and more open atd angles. Adults with broader hands have more arches. Taller individuals with larger hands present higher a-b ridge counts and leaner subjects with long narrow hands, closer atd angles. The correlation of physique and dermatoglyphics is small but if verified, suggests that at early fetal stages, factors responsible for the establishment of dermatoglyphic patterns interact with genetic determinants of adult shape that are already active.

Adult↗
PubMed1982

Migration and genetic infrastructure of the Central American Guaymi and their affinities with other tribal groups.

New genetic data on 40 red cell enzymes, antigenic blood groups, and serum proteins representing 42 separate loci, are reported for two Guaymi communities in Southeastern Costa Rica. These two settlements, Limoncito and Abrojo, are of recent origin, having been established by Panamanian migrants in the last 50 years. Detailed data on the provenance of these migrants permits an analysis of how these settlement patterns differ from those typical of less acculturated Amerindians from the lowlands of South America. The genetic compositions of these two communities are compared with those of previous Panamanian Guaymi samples, and several points are established: (1) One of the localities, Limoncito, contains families from both Guaymi dialect groups (eastern and western), and the allelic frequencies are intermediate between those of the dialect groups. (2) The other settlement, Abrojo, is quite similar to the western Guaymi, as expected from historical reconstruction of its antecedents. (3) In general, the degree of infratribal genetic diversity is less than that found in lowland South American tribes, and the difference may be due to a diffuse settlement pattern among the Guaymi. (4) The Guaymi are also compared genetically with other tribes in low Central America and northern South America, and appear to be similar to their immediate Chibcha neighbors to the east and west. The implications of a pair of "private polymorphisms" are discussed in the context of the time of dialectic and tribal divergence in this zone.

Alleles↗
PubMed1982

Glucose tolerance in two unacculturated Indian tribes of Brazil.

Plasma levels of glucose, insulin, growth hormone, and pancreatic polypeptide in response to a standard oral glucose load were studied in the Yanomama and the Marubo, two relatively unacculturated Amerindian tribes of the Brazilian Amazon. The findings in the two tribes differed significantly from each other and in the degree of deviation from control subjects. The average responses in both tribes differed significantly from those of age- and sex-matched Caucasoid control subjects studied in Ann Arbor, Michigan; however, of the two tribes, the Marubo, the more acculturated group, resembled the controls more closely. Plasma concentrations of glucose and the hormones at three time points (fasting, 1 h, 2 h) were compared by means of a multivariate analysis. When the Marubo were compared with the control subjects, the only highly significant difference was in the plasma glucose concentrations (all three points were higher in the Marubo); however, the Yanomama differed significantly from the control subjects with respect to all four plasma indicators (p less than 0.05). Unlike the Marubo, the Yanomama showed no significant rise in plasma glucose at 1 h and no decrease at 2 h. Neither tribe exhibited the bimodality of the 2 h glucose value characteristic of acculturated Amerindians, such as the Pima, but the samples studied were small.

Adolescent↗
PubMed1982

A phylogeny for the principal alleles of the human phosphoglucomutase-1 locus.

The results of phosphoglucomutase-1 (PGM1) typings by starch gel electrophoresis and subtypings by isoelectric focusing are presented for a sample of Japanese. A distinction made on the basis of isoelectric focusing (termed "+" and "-") is nonrandomly associated with each of the products of the four most common electrophoretic alleles (PGM1(1), PGM1(2), PGM1(3), and PGM1(7). The isoelectric trait cosegregates with the allele; the degree of nonrandomness of the association varies from allele to allele. Thus, the four alleles become eight. On the basis of these facts plus the additive nature of the pI differences between allele products and the geographical distribution of the alleles, an allele phylogeny can be constructed. This postulates that the eight alleles may be explained by three nucleotide substitutions involving the stem allele plus four intragenic recombinations between these substitutions. The potential of intragenic recombination as a cause of mutation has been insufficiently appreciated.

Alleles↗
PubMed1982

Identifying risk factors for diabetes in first degree relatives of non-insulin dependent diabetic patients.

Glucose tolerance test data on 794 first-degree relatives of diabetics in pedigrees ascertained through non-insulin dependent diabetes mellitus from southeastern Michigan were used to identify risk factors for diabetes. The general risk factors, age and obesity, were important in predicting diabetes at initial visit, although the predicted risk curves were very different from males and females. In predicting diabetes at initial visit, the number of affected sibs contributed more to the logistic regression than did the number of affected parents. Among a group of 393 individuals who were followed up for a mean of eight years, the initial glucose tolerance test response was the best single predictor of being diabetic on follow-up. These results suggest there may be a strong within-generational component which influences both the quantitative test response and the risk to diabetes. This component may reflect environmental factors influencing glucose tolerance among sibs and, as such, should be considered when studying the genetics of diabetes.

Adolescent↗