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Biomedical subjects

J A Phillips

Publications and source records attributed to J A Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1990

Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20.

The structural genes for human prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NPII; ARVP) locus and prepro-oxytocin-neurophysin-I (prepro-OT-NPI; OT) locus are closely linked separated by only 12 kilobasepairs of DNA. These two loci have been assigned to chromosome 20 by previous studies of somatic cell hybrids. We used Southern blots to analyze a restriction fragment length polymorphism detected by a probe for prepro-OT-NPI to determine the linkage relationships for the ARVP/OT loci using samples from the Centre d'Etude du Polymorphisme Humain (Paris, France) collection of families. The ARVP/OT loci demonstrated extremely close linkage with the prodynorphin (PDYN) locus, with no recombinants (theta of 0) and a log10 odds score of 5.2. Previous observations have shown the ARVP and PDYN peptides to be coexcreted in the same neurosecretory granules of some pituitary axons and that increased transcription of both genes occurs with osmotic stimulation. The combined ARVP/PT/PDYN group was also found to demonstrate linkage with other anonymous DNA segments on chromosome 20, including D20S4, D20S5, and D20S6. Using multilocus linkage analysis, the ARVP/OT loci map to the distal short arm of chromosome 20 about 15 centimorgans toward the telomere from the D20S5 locus, which is located near the middle of the short arm at 20p 12.21. These linkage relationships establish that the secretory and transcriptional associations of ARVP and PDYN extend to a close physical relationship in the human genome. Furthermore, the restriction fragment length polymorphism detected by these loci can serve as accurate markers in segregation studies of putative defects involving the OT, ARVP, or PDYN loci as well as provide a tool for studying the location of other genes, such as GH-releasing hormone.

Arginine Vasopressin↗
PubMed1990

Effect of pyridoxine on the disposition and lymphopenic effects of 2-acetyl-4(5)-tetrahydroxybutyl imidazole in the rat.

1. 2-Acetyl-4(5)-tetrahydroxybutyl imidazole (THI) administered orally to rats markedly decreased the peripheral blood lymphocyte count within 16-24 h. The lymphopenic effect of THI was prevented by co-administration of pyridoxine. 2. 14C-THI, administered orally, was absorbed in a dose-dependent manner and excreted unmetabolized. These processes were not affected by co-administration of pyridoxine. 3. In contrast, the rate of excretion of 14C-THI administered i.v. was increased by both dietary and parenterally-administered pyridoxine, and pyridoxine decreased the amount of radiolabel associated with lymphoid tissues. 4. The results show that the lymphopenic effect of THI is not sustained once it is excreted, and indicate that pyridoxine and THI may compete for the same binding site in lymphoid tissues.

Animals↗
PubMed1989

Synthesis and expression of the gene encoding human interleukin-3.

To perform structure-function studies of human interleukin-3 (hIL-3) we have synthesized a cDNA encompassing the complete coding region of 484 bp. The strategy we employed involved construction of the cDNA in four sections. Each fragment contained six to ten oligodeoxyribonucleotides. Unique restriction sites were engineered to flank the natural sequence for cloning. Naturally occurring restriction sites were placed internally to these, to allow ligation of the four fragments. The gene was cloned into a modified pJL4 vector and expressed in COS cells. Biological assays of supernatants collected from these cells, for both mature cell function and proliferative activity, showed that synthetic hIL-3 had the same activity as that previously determined for recombinant hIL-3.

Animals↗
PubMed1989

Familial aplasia of the cerebellar vermis. Possible X-linked dominant inheritance.

To our knowledge, this is the third (possibly the fourth) description of a family with partial aplasia of the cerebellar vermis. The major clinical features are normal intelligence, delayed achievement of motor milestones, truncal ataxia, and nystagmus. Twelve of 14 affected individuals are female. The two affected males were more severely affected than were their female relatives. These findings along with apparently increased fetal wastage suggest that an X-linked rather than an autosomal dominant mode of inheritance may be responsible for this disorder.

Ataxia↗
PubMed1989

The effect of 2-acetyl-4-tetrahydroxybutylimidazole on lymphocyte subsets in peripheral blood of the rat.

A constituent of Ammonia Caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), is known to cause a reduction in the number of circulating lymphocytes when fed to rats. In the present study the effect of giving THI 1 mg/kg by gavage daily for 7 days on the numbers of lymphocytes in subsets has been monitored in peripheral blood. Both immunoglobulin light chain-bearing B-cells (MARK-1+) and CD5 marker-bearing T-cells (OX-19+) were reduced in number within 1 day of treatment. Within the pan-T-cell population, Class II MHC reactive helper T-lymphocytes (W3/25-) were more reduced than the Class I MHC reactive cytotoxic/suppressor T cells (OX-8+). The number of null cells (MARK-1-, OX-19-) was not affected; the majority of these cells appeared to be large granular lymphocytes.

Animals↗
PubMed1989

Protein kinase C: a new linkage marker for growth hormone and for COL1A1.

An expanded linkage group on the long arm of human chromosome 17 is reported. Using the CEPH panel of DNAs and restriction fragment length polymorphism (RFLP) markers for the centromere locus (D17Z1), growth hormone (GH1), collagen type I alpha 1 (COL1A1), and protein kinase C-alpha polypeptide (PKCA) loci, theta values of 0.03, 0.11, and 0.23 were found between PKCA and GH1, PKCA and COL1A1, and PKCA and D17Z1, respectively. The theta values calculated for GH1 versus COL1A1 or D17Z1 were 0.11 and 0.23, respectively. Sex-specific recombination rates were calculated for the best likelihood order and demonstrate female recombination greater than male recombination. Therefore, the loci studied span a map region of approximately 30 cm between 17cen and 17q24, with the most likely gene order being D17Z1-COL1A1-PKCA-GH1.

Alleles↗
PubMed1989

Prenatal diagnosis of sickle cell anemia. Hemoglobin electrophoresis versus DNA analysis.

The prenatal diagnosis of sickle cell anemia (hemoglobin SS) can be established by DNA analysis using two highly sensitive techniques (Southern blot and polymerase chain reaction [PCR]). Hemoglobin electrophoresis provides a third, simpler and more rapid, technique to analyze blood from a fetus at risk for sickle cell anemia. The authors present examples of prenatal diagnostic studies using both DNA analysis techniques and hemoglobin electrophoresis. Hemoglobin electrophoresis of fetal hemolysate can provide a simple and rapid alternative method to PCR analysis for the prenatal exclusion of sickle cell anemia, and it is especially useful in cases in which rapid results are needed because of advanced gestational age.

Adult↗
PubMed1989

Discordant immune and growth response to pituitary and biosynthetic growth hormone in siblings with isolated growth hormone deficiency type IA.

Two brothers with familial isolated growth hormone deficiency type IA homozygous for the same 6.7 kb deletion on chromosome 17 including the growth hormone gene were intermittently treated with various forms of hGH for more than 7 years. While the elder brother (Patient 1) showed a good growth response to pituitary hGH, the younger one (Patient 2) developed high titre growth blocking hGH antibodies early in the course of treatment and grew only 2.2-3.9 cm/year on a hGH dose of 12-26 IU/m2 per week. When the younger brother was changed to a higher dose (33 IU/m2 per week) of biosynthetic methionyl hGH he had striking catch-up growth and he has subsequently maintained a height velocity of 10.0 cm/year for the last 2 years. During this time his antibody titres have decreased over 1000-fold. These findings demonstrate that therapy with biosynthetic methionyl hGH may provide an effective form of treatment for subjects with isolated growth hormone deficiency type IA who do not grow in response to native hGH, and imply that biosynthetic methionyl hGH may be less antigenic than pituitary derived hGH.

Adolescent↗
PubMed1989

Linkage analysis of neurofibromatosis type I, using chromosome 17 DNA markers.

The gene for von Recklinghausen neurofibromatosis type 1 (NF1) has recently been mapped to the pericentromeric region of human chromosome 17. To further localize the NF1 gene, linkage analysis using chromosome 17 DNA markers was performed on 11 multigeneration families with 175 individuals, 57 of whom were affected. The markers used were D17Z1 (p17H8), D17S58 (EW301), D17S54 (EW203), D17S57 (EW206), D17S73 (EW207), CRI-L946, HOX-2, and growth hormone. Tight linkage was found between NF1 and D17Z1, D17S58, and D17S57 with a recombination fraction of zero. One recombinant was detected between NF1 and D17S73, showing linkage with a 10% recombination fraction. No linkage was detected between NF1 and CRI-L946 or between HOX-2 and growth hormone. Our data are consistent with the proposed gene order pter D17S58-D17Z1-NF1-D17S57-D17S73 qter.

Chromosome Mapping↗
PubMed1989

Inherited hypercoagulable states in children.

Disorders that predispose children to venous thrombosis include inherited abnormalities of antithrombin III, protein S, protein C, fibrinogen, and plasminogen. Arterial thrombosis may result from disorders that produce endothelial damage, abnormal vascular flow, or increased platelet aggregation. We present here a case of a child who had recurrent thromboses and discuss the evaluation and management of such patients.

Adult↗
PubMed1988

Two patients with ring chromosome 15 syndrome.

We report on 2 patients (3 1/2 year-old-male and 6-year-old female) with the ring 15 chromosome syndrome and speech delays and review 25 cases from the literature. The main characteristics of this syndrome include growth retardation (100%), variable mental retardation (95%), microcephaly (88%), hypertelorism (46%), and triangular facies (42%). Other frequent findings include delayed bone age (75%), brachydactyly (44%), speech delay (39%), frontal bossing (36%), anomalous ears (30%), café-au-lait spots (30%), cryptorchidism (30%), and cardiac abnormalities (30%). The average age at diagnosis was 8.1 years. The average maternal and paternal age at the time of birth was 28 and 31 years, respectively.

Abnormalities, Multiple↗
PubMed1988

The pineal complex, aggressive behavior and thermoregulation in curly-tailed lizards, Leiocephalus carinatus.

Male Leiocephalus carinatus exhibited five types of aggressive displays, two of which were used to quantify aggression in paired encounters. After the dominant and subordinate lizard were identified, the area over parietal eye/pineal gland of the latter was shielded. This resulted in the subordinate lizard selecting higher body temperatures, exhibiting more assertive displays toward the dominant lizard, and increasing its frequency of use of a heat source that was the limited resource, as defined in the test arena. All of these responses required 4-6 days to be expressed and were reversed when the shield was removed. The results suggest that the responses are hormonally-controlled, and possibly represent an interaction between the pineal complex and discrete brain nuclei and/or the thyroid gland.

Aggression↗
PubMed1988

Molecular basis of human growth hormone gene deletions.

Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients. In eight unrelated subjects homozygous for 6.7-kilobase (kb) deletions, the breakpoints are within two blocks of highly homologous DNA sequences that lie 5' and 3' to the GH1 gene. In seven of these eight cases, the breakpoints map within a 1250-base-pair (bp) region composed of 300-bp Alu sequences of 86% homology and flanking non-Alu sequences that are 600 and 300 bp in length and are of 96% and 88% homology, respectively. In the eighth patient, the breakpoints are 5' to these Alu repeats and are most likely within a 700-bp region of 96% homologous DNA sequences. In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained within a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1). Together, these results indicate that the presence of highly homologous DNA sequences flanking GH1 predispose to recurrent unequal recombinational events presumably through chromosomal misalignment.

Base Sequence↗
PubMed1988

Secretory effects of kinins on colonic epithelium in relation to prostaglandins released from cells of the lamina propria.

1. Sheets of muscle-stripped rat and rabbit colon with epithelium intact or removed were mounted in Ussing-type chambers for recording of transepithelial p.d., resistance and short circuit current (Isc), and measurement by radioimmunoassay (RIA) of the release of prostaglandins into serosal and mucosal bathing solutions. 2. In epithelial-intact preparations prostaglandin E2 (PGE2), PGE1, PGF2 alpha, U46619 and prostacyclin (10(-7)-10(-6) M) caused increases in Isc and transepithelial p.d., in (approximate) descending order of potency. Epithelial-removed preparations did not exhibit any transepithelial p.d. 3. In epithelial-intact preparations, lysyl-bradykinin (LBk) applied serosally but not mucosally caused increased p.d. and release of PGE2 (and to a lesser extent other prostaglandins) into serosal but not mucosal bathing solutions. In epithelial-removed tissues, responsiveness to LBk was maintained, but it did not exhibit 'sidedness', i.e. LBk was effective when applied on either side and PGE2 release occurred into both compartments. 4. Indomethacin and other non steroidal anti-inflammatory drugs (NSAIDs) abolished the LBk-induced p.d. and reduced PGE2 release if applied serosally but not mucosally in epithelial-intact preparations. In epithelial-removed tissues, indomethacin added to either side abolished prostaglandin release into both compartments. 5. Calcium removal from serosal but not mucosal bathing solution (Ca2+-free EGTA Krebs) abolished p.d. generation by LBk in epithelial-intact preparations, and reduced PGE2 release in rabbit but not rat colon. Similarly, in epithelial-removed preparations, calcium removal did not affect kinin-induced PGE2 generation in rat but strongly attenuated it in rabbit colon. 6. We conclude that (i) kinins activate the arachidonate cascade principally by interactions with cells in the subepithelial (lamina propria) layer, rather than with the epithelial cells themselves, (ii) PGE2 contributes substantially to the kinin-induced increase of transepithelial p.d. as a messenger released from kinin-responsive subepithelial cells and acting on the basolateral pole of the epithelial cells, (iii) the apparent sidedness of colonic epithelium in terms of responses to kinins, NSAIDs and calcium removal is due to the barrier properties of the epithelial cell layer, and (iv) there are differences in calcium sequestration and apparent calcium dependence of prostaglandin biosynthesis between rat and rabbit colonic subepithelial cells.

Animals↗