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T Jenkins

Publications and source records attributed to T Jenkins.

At least 19 recordsLinked to original sources
PubMed2006

Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy cows: III. Fatty acid distribution.

Our objective was to examine effects of exogenous bovine somatotropin (bST), pregnancy, and dietary fatty acids on fatty acid distribution in various tissues of lactating dairy cows. Two diets were fed, starting about 17 d in milk (DIM), in which oil of whole cottonseed (control diet) was compared with a calcium salt of fish oil-enriched lipid (FO; 1.9% of dietary DM). Starting at 44 +/- 5 DIM, ovulation was synchronized with a presynchronization plus Ovsynch protocol (d 0 = time of synchronized ovulation). Some cows were inseminated (77 +/- 12 DIM) to create a pregnant group. On d 0 and 11, cows received bST (500 mg) or no bST, and were killed on d 17 (94 +/- 12 DIM). Number of cows in control group was 5 bST-treated cyclic (bST-C), 5 non-bST-treated cyclic (no bST-C), 4 bST-treated pregnant (bST-P), and 5 non-bST-treated pregnant (no bST-P) cows; and for the FO diet: 4 bST-treated (bST-FO-C) and 5 non-bST-treated cyclic (no bST-FO-C) cows. At slaughter, samples of endometrium, liver, muscle, s.c. adipose, internal adipose, and mammary gland were collected. Milk was collected at 75 +/- 5 DIM. Gas chromatography was used to determine fatty acid percentages in tissues and milk fat. Endometrium from the cows fed FO had increased proportions of C20:5 and C22:6, whereas C20:4 was decreased. Injections of bST reduced both C18:2 and the n-6:n-3 ratio, but increased C22:6 in endometrium of cyclic control-fed, but not pregnant cows. In addition, FO decreased the n-6:n-3 ratio in all tissues and milk fat except for s.c. and internal adipose tissue. Cows fed FO also had increased C18:3, C20:5, and C22:6 in the liver and mammary tissue, and C18:3 and C22:6 were increased in the milk fat. The FO diet decreased the Delta9-desaturase index [(product of Delta9-desaturase]/(product of Delta9-desaturase + substrate of Delta9-desaturase]; DIX) in muscle and s.c. tissues, accompanied by an increase in saturated fatty acid (SFA) percentage. In addition, FO diet decreased DIX in the endometrium. In mammary and internal adipose tissues, bST increased DIX in cyclic control-fed cows, whereas bST decreased DIX in FO-fed cows, with no difference in the concentration of SFA and UNSFA. Cis-9, trans-11 conjugated linoleic acid was increased in milk fat, but decreased in the muscle and s.c. adipose tissue of FO-fed cows. The FO-enriched lipid, bST treatment, and early pregnancy can alter fatty acid percentages and distributions that may alter tissue functionality and functional nutrients of consumer products.

Adipose Tissue↗
PubMed2005

Evidence for a multivalent interaction of symmetrical, N-linked, lidocaine dimers with voltage-gated Na+ channels.

The interaction of symmetrical lidocaine dimers with voltage-gated Na+ channels (VGSCs) was examined using a FLIPR membrane potential assay and voltage-clamp. The dimers, in which the tertiary amines of the lidocaine moieties are linked by an alkylene chain (two to six methylene units), inhibited VGSC activator-evoked depolarization of cells heterologously-expressing rat (r) Na(v)1.2a, human (h) Na(v)1.5, and rNa(v)1.8, with potencies 10- to 100-fold higher than lidocaine (compound 1). The rank order of potency (C4 (compound 4) > C3 (compound 3) > or = C2 (compound 2) = C5 (compound 5) = C6 (compound 6) >> compound 1) was similar at each VGSC. Compound 4 exhibited strong use-dependent inhibition of hNa(v)1.5 with pIC50 values < 4.5 and 6.0 for tonic and phasic block, respectively. Coincubation with local anesthetics but not tetrodotoxin attenuated compound 4-mediated inhibition of hNa(v)1.5. These data suggest that the compound 4 binding site(s) is identical, or allosterically coupled, to the local anesthetic receptor. The dissociation rate of the dimers from hNa(v)1.5 was dependent upon the linker length, with a rank order of compound 1 > compound 5 = compound 6 > compound 2 >> compound 3. The observation that both the potency and dissociation rate of the dimers was dependent upon linker length is consistent with a multivalent interaction at VGSCs. hNa(v)1.5 VGSCs did not recover from inhibition by compound 4. However, "chase" with free local anesthetic site inhibitors increased the rate of dissociation of compound 4. Together, these data support the hypothesis that compound 4 simultaneously occupies two binding sites on VGSCs, both of which can be bound by known local anesthetic site inhibitors.

Anesthetics, Local↗
PubMed2004

Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa.

BACKGROUND: Lipoid proteinosis (LiP) is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LiP. Since the early 1970s it has been recognized that South Africa has one of the largest groups of LiP patients worldwide, suggesting a probable founder effect. As LiP patients present with considerable clinical variability, this group of patients offers a unique opportunity for genotype-phenotype correlation. OBJECTIVES: To assess the clinical features and the molecular basis of LiP in patients from the Namaqualand area of the Northern Cape province of South Africa and to examine molecular evidence for a founder effect. SUBJECTS AND METHODS: The LiP patient cohort consisted of 29 Coloured patients from Namaqualand and a further seven Caucasoid patients from other areas of South Africa. The control group included 100 healthy geographically and ethnically matched individuals from Namaqualand. Samples were collected after informed consent and with ethics committee approval from the University of the Witwatersrand. LiP patients were examined clinically and a structured recording sheet was completed. A brief neurological evaluation was also performed. The LiP founder effect was investigated at the molecular level by ECM1 mutation detection and haplotype analysis. RESULTS: The most consistent clinical signs for a diagnosis of LiP in this group were a hoarse voice and thickened sublingual frenulum leading to restricted tongue movement. Homozygosity for a nonsense mutation in exon 7 of the ECM1 gene, Q276X, was identified in all patients (Coloured and Caucasoid). Despite this genetic homogeneity, considerable clinical variability in skin presentation and psychiatric involvement was observed. Haplotype analysis using markers from a 9.98-Mb region around the ECM1 locus confirmed the founder effect with a founder core haplotype, 19-Q276X-12 (ND1-ECM1-D1S2343), in all but four LiP-associated alleles (n = 58). A LiP carrier rate of 1 in 9 was observed among the 100 Namaqualand controls, predicting a LiP incidence of 1 in 324 in this community. CONCLUSIONS: Although several consistent clinical features in LiP patients homozygous for the Q276X mutation in the ECM1 gene were observed, there remains considerable clinical variability. This suggests the action of genetic and environmental modifiers of disease severity. Strong molecular evidence supports a single founder effect for the high prevalence of LiP in South Africans, both Coloured and Caucasoid.

Adolescent↗
PubMed2001

In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified.

In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; theta=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype.

Albinism, Oculocutaneous↗
PubMed2001

Human DNA sequence variation in a 6.6-kb region containing the melanocortin 1 receptor promoter.

An approximately 6.6-kb region located upstream from the melanocortin 1 receptor (MC1R) gene and containing its promoter was sequenced in 54 humans (18 Africans, 18 Asians, and 18 Europeans) and in one chimpanzee, gorilla, and orangutan. Seventy-six polymorphic sites were found among the human sequences and the average nucleotide diversity (pi) was 0.141%, one of the highest among all studies of nuclear sequence variation in humans. Opposite to the pattern observed in the MC1R coding region, in the present region pi is highest in Africans (0.136%) compared to Asians (0.116%) and Europeans (0.122%). The distributions of pi, theta, and Fu and Li's F-statistic are nonuniform along the sequence and among continents. The pattern of genetic variation is consistent with a population expansion in Africans. We also suggest a possible phase of population size reduction in non-Africans and purifying selection acting in the middle subregion and parts of the 5' subregion in Africans. We hypothesize diversifying selection acting on some sites in the 5' and 3' subregions or in the MC1R coding region in Asians and Europeans, though we cannot reject the possibility of relaxation of functional constraints in the MC1R gene in Asians and Europeans. The mutation rate in the sequenced region is 1.65 x 10(-9) per site per year. The age of the most recent common ancestor for this region is similar to that for the other long noncoding regions studied to date, providing evidence for ancient gene genealogies. Our population screening and phylogenetic footprinting suggest potentially important sites for the MC1R promoter function.

Animals↗
PubMed2001

Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1.

Human DNA variation is currently a subject of intense research because of its importance for studying human origins, evolution, and demographic history and for association studies of complex diseases. A approximately 10-kb region on chromosome 1, which contains only four small exons (each <155 bp), was sequenced for 61 humans (20 Africans, 20 Asians, and 21 Europeans) and for 1 chimpanzee, 1 gorilla, and 1 orangutan. We found 52 polymorphic sites among the 122 human sequences and 382 variant sites among the human, chimpanzee, gorilla, and orangutan sequences. For the introns sequenced (8,991 bp), the nucleotide diversity (pi) was 0.058% among all sequences, 0.076% among the African sequences, 0.047% among the Asian sequences, and 0.045% among the European sequences. A compilation of data revealed that autosomal regions have, on average, the highest pi value (0.091%), X-linked regions have a somewhat lower pi value (0.079%), and Y-linked regions have a very low pi value (0.008%). The lower polymorphism in the present region may be due to a lower mutation rate and/or selection in the gene containing these introns or in genes linked to this region. The present region and two other 10-kb noncoding regions all show a strong excess of low-frequency variants, indicating a relatively recent population expansion. This region has a low mutation rate, which was estimated to be 0.74 x 10 per nucleotide per year. An average estimate of approximately 12,600 for the long-term effective population size was obtained using various methods; the estimate was not far from the commonly used value of 10,000. Fu and Li's tests rejected the assumption of an equilibrium neutral Wright-Fisher population, largely owing to the high proportion of low-frequency variants. The age of the most recent common ancestor of the sequences in our sample was estimated to be more than 1 Myr. Allowing for some unrealistic assumptions in the model, this estimate would still suggest an age of more than 500,000 years, providing further evidence for a genetic history of humans much more ancient than the emergence of modern humans. The fact that many unique variants exist in Europe and Asia also suggests a fairly long genetic history outside of Africa and argues against a complete replacement of all indigenous populations in Europe and Asia by a small Africa stock. Moreover, the ancient genetic history of humans indicates no severe bottleneck during the evolution of humans in the last half million years; otherwise, much of the ancient genetic history would have been lost during a severe bottleneck. We suggest that both the "Out of Africa" and the multiregional models are too simple to explain the evolution of modern humans.

Africa↗
PubMed2001

Comparison of outcome predictions made by physicians, by nurses, and by using the Mortality Prediction Model.

BACKGROUND: Critical care nurses must collaborate with physicians, patients, and patients' families when making decisions about aggressiveness of care. However, few studies address nurses' ability to predict outcomes. OBJECTIVES: To compare predictions of survival outcomes made by nurses, by physicians, and by using the Mortality Prediction Model. METHODS: Predictions of survival and function and attitudes toward aggressiveness of care based on the predictions were recorded on questionnaires in the emergency department by emergency and intensive care unit physicians and by intensive care unit nurses at the time of admission to the unit between February and September 1995 for 235 consecutive adult nontrauma patients. Scores on the Mortality Prediction Model were calculated on admission. Data on 85 of the 235 patients were analyzed by using descriptive, chi 2, and correlational statistics. Nurses' predictions of function were compared with patients' actual outcomes 6 months after admission. RESULTS: Nurses' predictions of survival were comparable to those of emergency physicians and superior to those obtained by using the objective tool. Years of nursing experience had no relationship to attitudes toward aggressiveness of care. Nurses accurately predicted functional outcomes in 52% of the followed-up cases. Intensive care physicians were more accurate than nurses and emergency physicians in predicting survival. All predictions made by clinicians were superior to those obtained by using the model. CONCLUSIONS: Nurses can predict survival outcomes as accurately as physicians do. Greater sensitivity and specificity are necessary before clinical judgment or predictive tools can be considered as screens for determining aggressiveness of care.

Adolescent↗
PubMed2000

Lactase haplotype diversity in the Old World.

Lactase persistence, the genetic trait in which intestinal lactase activity persists at childhood levels into adulthood, varies in frequency in different human populations, being most frequent in northern Europeans and certain African and Arabian nomadic tribes, who have a history of drinking fresh milk. Selection is likely to have played an important role in establishing these different frequencies since the development of agricultural pastoralism approximately 9,000 years ago. We have previously shown that the element responsible for the lactase persistence/nonpersistence polymorphism in humans is cis-acting to the lactase gene and that lactase persistence is associated, in Europeans, with the most common 70-kb lactase haplotype, A. We report here a study of the 11-site haplotype in 1,338 chromosomes from 11 populations that differ in lactase persistence frequency. Our data show that haplotype diversity was generated both by point mutations and recombinations. The four globally common haplotypes (A, B, C, and U) are not closely related and have different distributions; the A haplotype is at high frequencies only in northern Europeans, where lactase persistence is common; and the U haplotype is virtually absent from Indo-European populations. Much more diversity is seen in sub-Saharan Africans than in non-Africans, consistent with an "Out of Africa" model for peopling of the Old World. Analysis of recent recombinant haplotypes by allele-specific PCR, along with deduction of the root haplotype from chimpanzee sequence, allowed construction of a haplotype network that assisted in evaluation of the relative roles of drift and selection in establishing the haplotype frequencies in the different populations. We suggest that genetic drift was important in shaping the general pattern of non-African haplotype diversity, with recent directional selection in northern Europeans for the haplotype associated with lactase persistence.

Africa South of the Sahara↗
PubMed2000

Structure-activity relationships of a series of pyrrolo[3,2-d]pyrimidine derivatives and related compounds as neuropeptide Y5 receptor antagonists.

Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. Pharmacological data suggests that the Y5 receptor subtype contributes to the effects of NPY on appetite, and therefore a Y5 antagonist might be a useful therapeutic agent for the treatment of obesity. In attempts to identify potential Y5 antagonists, a series of pyrrolo[3, 2-d]pyrimidine derivatives was prepared and evaluated for their ability to bind to Y5 receptors in vitro. We report here the synthesis and initial structure-activity relationship investigations for this class of compounds. The target compounds were prepared by a variety of synthetic routes designed to modify both the substitution and the heterocyclic core of the pyrrolo[3,2-d]pyrimidine lead 1. In addition to identifying several potent Y5 antagonists for evaluation as potential antiobesity agents, a pharmacophore model for the human Y5 receptor is presented.

Anti-Obesity Agents↗
PubMed2000

Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22.

Human DNA sequence variation data are useful for studying the origin, evolution, and demographic history of modern humans and the mechanisms of maintenance of genetic variability in human populations, and for detecting linkage association of disease. Here, we report worldwide variation data from a approximately 10-kilobase noncoding autosomal region. We identified 75 variant sites in 64 humans (128 sequences) and 463 variant sites among the human, chimpanzee, and orangutan sequences. Statistical tests suggested that the region is selectively neutral. The average nucleotide diversity (pi) across the region was 0.088% among all of the human sequences obtained, 0.085% among African sequences, and 0.082% among non-African sequences, supporting the view of a low nucleotide diversity ( approximately 0.1%) in humans. The comparable pi value in non-Africans to that in Africans indicates no severe bottleneck during the evolution of modern non-Africans; however, the possibility of a mild bottleneck cannot be excluded because non-Africans showed considerably fewer variants than Africans. The present and two previous large data sets all show a strong excess of low frequency variants in comparison to that expected from an equilibrium population, indicating a relatively recent population expansion. The mutation rate was estimated to be 1.15 x 10(-9) per nucleotide per year. Estimates of the long-term effective population size N(e) by various statistical methods were similar to those in other studies. The age of the most recent common ancestor was estimated to be approximately 1.29 million years ago among all of the sequences obtained and approximately 634,000 years ago among the non-African sequences, providing the first evidence from a noncoding autosomal region for ancient human histories, even among non-Africans.

Animals↗
PubMed2000

Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins.

Two dinucleotide short tandem-repeat polymorphisms (STRPs) and a polymorphic Alu element spanning a 22-kb region of the PLAT locus on chromosome 8p12-q11.2 were typed in 1,287-1,420 individuals originating from 30 geographically diverse human populations, as well as in 29 great apes. These data were analyzed as haplotypes consisting of each of the dinucleotide repeats and the flanking Alu insertion/deletion polymorphism. The global pattern of STRP/Alu haplotype variation and linkage disequilibrium (LD) is informative for the reconstruction of human evolutionary history. Sub-Saharan African populations have high levels of haplotype diversity within and between populations, relative to non-Africans, and have highly divergent patterns of LD. Non-African populations have both a subset of the haplotype diversity present in Africa and a distinct pattern of LD. The pattern of haplotype variation and LD observed at the PLAT locus suggests a recent common ancestry of non-African populations, from a small population originating in eastern Africa. These data indicate that, throughout much of modern human history, sub-Saharan Africa has maintained both a large effective population size and a high level of population substructure. Additionally, Papua New Guinean and Micronesian populations have rare haplotypes observed otherwise only in African populations, suggesting ancient gene flow from Africa into Papua New Guinea, as well as gene flow between Melanesian and Micronesian populations.

Africa South of the Sahara↗
PubMed2000

Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes.

Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level. Admixture estimates suggested low levels of European Y-chromosome gene flow into Ashkenazi and Roman Jewish communities. A multidimensional scaling plot placed six of the seven Jewish populations in a relatively tight cluster that was interspersed with Middle Eastern non-Jewish populations, including Palestinians and Syrians. Pairwise differentiation tests further indicated that these Jewish and Middle Eastern non-Jewish populations were not statistically different. The results support the hypothesis that the paternal gene pools of Jewish communities from Europe, North Africa, and the Middle East descended from a common Middle Eastern ancestral population, and suggest that most Jewish communities have remained relatively isolated from neighboring non-Jewish communities during and after the Diaspora.

Base Sequence↗
PubMed2000

Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families.

Recent reports have strongly linked markers near the alpha-7 nicotinic cholinergic receptor subunit gene on human chromosome 15q13-q14 to a sensory gating deficit common in schizophrenics, and have shown positive though non-significant results linking this region to the primary phenotype of schizophrenia in a sample of North American families. We therefore tested for linkage between markers in this region of chromosome 15q and schizophrenia in a sample of 15 multiply affected and 5 single case families with schizophrenia drawn from the Bantu-speaking black population of South Africa. An initial replication using markers from the original study gave an affected-only LOD score maximum of 1.08 under a recessive model at Theta=0.00 for D15S1360, a dinucleotide polymorphism found on the same YAC as the alpha-7 receptor gene. Nonparametric affected-only multipoint analysis gave a Z-score of 1. 29, P=0.098, for D15S1360, and Z=1.45, p=0.075 for D15S118. We then increased the resolution of the map with an extended set of 20 markers. Again, two peaks were observed, with NPL scores of 1.81, p=0.037, at D15S1043 and 1.79 at D15S1360 and 1.80 at D15S1010, both p=0.037. Transmission disequilibrium testing of data from D15S1360 gave an allele-wise and genotype-wise chi(2) of 6.59, 2 df, p=0.037. Haplotype transmission disequilibrium testing using a restricted allele and haplotype set from D15S1043 and D15S1360 gave a global chi(2) of 10.647, 4 df, P=0.007, and a maximum chi(2) of 6.567, 1 df, P=0.004 for excess transmission of the 1.2 haplotype into affected offspring. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:196-201, 2000.

Bungarotoxins↗
PubMed2000

Y chromosome sequence variation and the history of human populations.

Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.

Africa↗
PubMed2000

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Genetics, Medical↗