Search PubMed⌕ Search

Biomedical subjects

J S Parks

Publications and source records attributed to J S Parks.

At least 127 records · Page 7Linked to original sources
PubMed1983

Structural variants of human growth hormone: biochemical, genetic, and clinical aspects.

Human growth hormone (hGH) is a mixture of peptides in which the major physiologic component is a single chain polypeptide of 191 residues with a molecular weight of 22,000 ("22K" form). The minor components differ from the 22K form in terms of mass (e.g. the 20K form, a single-chain peptide synthesized by deletion of residues 32-46 of the 22K isomer, and the 45K variant formed by aggregation of the 22K molecule), or of charge (e.g. the more acidic two-chain forms alpha 2 and alpha 3 which are generated by proteolytic deletion of residues 135-140 and 135-146 from the 22K variant). The minor components also differ from the 22K molecule in (a) their metabolic effects; (b) their capacity to bind to antiserum raised against the 22K form in a radioimmunoassay (RIA); and (c) their ability to bind to membrane receptors for the 22K hGH in a radioreceptor assay (RRA). Two genes, N and V, involved in the biosynthesis of hGH, are located on human chromosome 17. Heritable alterations of the N gene may cause deficiency of immunoreactive hGH and growth failure. A pathologic variant of hGH has also been identified which is indistinguishable from the 22K form on RIA, but which has low reactivity on hGH-RRA and low somatomedogenic activity. Several mechanisms to account for this bioinactive variant are discussed.

Child↗
PubMed1983

Metabolism of the serum amyloid A proteins (SSA) in high-density lipoproteins and chylomicrons of nonhuman primates (vervet monkey).

Serum amyloid protein (SAA) has been reported to be an apoprotein of high-density lipoprotein (HDL), but little is known concerning its metabolism. In this study, apoSAA was induced in nonhuman primate plasma HDL and thoracic duct lymph chylomicra by overnight chair restraint of the animals. There was a 3-6-fold increase in plasma HDL apoSAA in chair-restrained animals when compared with caged (control) animals. Lymph chylomicrons of chaired animals also contained significant amounts (approximately 20% of total protein) of apoSAA. For study of the metabolism of HDL apoSAA, animals were given injections of 131I-labeled lymph chylomicrons and autologous 125I-HDL. HDL were isolated from the plasma of recipient animals between 1 minute and 5 days after injection, and the specific activity of the apoSAA was determined. The turnover of apoSAA from plasma was biphasic, the initial phase having a t1/2 (0.39-0.48 days) similar regardless of the source (chylomicrons versus HDL) of the injected dose. The second phase of the turnover was significantly faster (t1/2 = 2.5 days) for apoSAA of 125I-HDL origin than that of 131I-chylomicron origin (t1/2 = 4.3 days). This difference also was suggested by the fractional catabolic rates (FCR) of 125I-HDL and 131I-chylomicron apoSAA (1.02 versus 0.74 d-1, respectively). From these studies it was concluded that 1) apoSAA can be rapidly induced in plasma HDL and lymph chylomicrons of nonhuman primates by chair restraint; 2) HDL apoSAA is catabolized more rapidly than HDL apoA-I and apoA-II; 3) and the catabolic rate of HDL apoSAA may be determined, in part, by its lipoprotein origin (chylomicrons versus HDL).

Amino Acid Sequence↗
PubMed1982

A gene deletion is responsible for absence of human chorionic somatomammotropin.

We have examined the human growth hormone (hGH) and human chorionic somatomammotropin (hCS) family of genes in genomic DNA from an individual with complete antenatal deficiency of hCS. Following digestion with a variety of bacterial restriction endonucleases, the DNA from this individual produced fewer fragments with homology to a radiolabeled hCS cDNA probe than did control DNA specimens. The patterns indicated that his DNA contained the normal hGH gene and an "hGH-like" gene, but lacked the hCS gene, a variant hGH gene, and another gene or genes with structural homology to hGH and hCS, which were present in all control DNA specimens. The findings were consistent with homozygosity for a gene deletion with a minimum length of 18.5 kb. Analysis of polymorphic restriction site variation related to the hGH and hCS gene cluster indicated that both parents and three older siblings were heterozygous for the deletion. The association between gene deletion and a normal growth pattern in this individual indicates that hCS and any other peptide hormones encoded by the variant hGH and the other related gene(s) that are deleted in this individual are not required for fetal or extrauterine growth.

Adolescent↗
PubMed1982

Genetic analysis of familial isolated growth hormone deficiency type I.

Nuclear DNA from individuals belonging to nine different families in which two sibs were affected with isolated growth hormone deficiency type I were studied by restriction endonuclease analysis. By using 32P-labeled human growth hormone or the homologous human chorionic somatomammotropin complementary DNA (cDNA) sequences as a probe, the growth hormone genes of affected individuals from all families yielded normal restriction patterns. Polymorphic restriction endonuclease sites (HincII and MspI), which are closely linked to the structural gene for growth hormone on chromosome 17, were used as markers in linkage analysis of DNA of family members. Of the nine affected sib pairs two were concordant, three were possibly concordant, and four were discordant for both linked markers. Since only concordant sib pairs would have inherited the same growth hormone alleles, further studies to identify mutations of the growth hormone genes should be limited to this subgroup. It is unlikely that the discordance observed in four of the sib pairs is due to recombination, because the polymorphic HincII site is only 116 base-pairs from the -26 codon of the growth hormone gene. Thus, in at least four of the nine families, the mutation responsible for isolated growth hormone deficiency is not within or near the structural gene for growth hormone on chromosome 17.

Chromosome Mapping↗
PubMed1982

Structural analysis of rodent growth hormone genes: application to genetic forms of hypopituitarism.

Analysis of GH gene structure in the mouse permits evolutionary comparisons with GH gene structure in the rat and provides information about the mechanism responsible for heritable deficiencies of anterior pituitary hormones. The little mutation in mice is analogous to autosomal recessive, isolated, partial deficiency of GH in man, whereas the Snell dwarf mutation is a model for autosomal recessive deficiency of GH, TSH, and PRL. Mouse cellular DNA was digested with the restriction enzymes Eco RI, Bam HI, Bgl II, Hind III, and Kpn I, singly and in combination. Gene sequences containing coding information for GH were detected by hybridization to a radiolabeled recombinant DNA probe complementary to a rat GH mRNA. The results of genomic restriction analysis indicate that there is a single type of mouse GH gene sequence per haploid genome with a length equal to or less than 32000 base pairs. The distances separating 6-base restriction sites close to the mouse GH gene differ from those close to the rat GH gene. A Kpn I site in the codons for amino acids 103 and 104 of rat GH is absent in the mouse gene. Restriction patterns of DNA from little and Snell dwarf mice did not differ from those of normal mice, indicating that these mutations do not involve deletions of the mouse GH gene.

Animals↗
PubMed1982

Different kinetic fates of apolipoproteins A-I and A-II from lymph chylomicra of nonhuman primates. Effect of saturated versus polyunsaturated dietary fat.

Monkeys fed polyunsaturated fat had significantly lower plasma cholesterol (186 +/- 18 vs. 276 +/- 31 mg/dl) and high density lipoprotein (HDL) mass concentrations (466 +/- 28 vs. 518 +/- 34 mg/dl) than did animals fed saturated fat. Plasma apoA-I concentrations also were significantly lower and apoA-II levels were generally, though not significantly, lower in the group fed polyunsaturated fat. In vivo reinjection studies, using thoracic duct lymph chylomicra labeled with (131)I and HDL labeled with (125)I, were done in order to study the mechanism of plasma HDL-lowering by polyunsaturated dietary fat. The peak specific activity (SA) of HDL apoA-I derived from (131)I-labeled chylomicra occurred at 3 hr after injection (172 +/- 11% of 1 min S.A.) and then an exponential decay occurred indicative of a precursor-product relationship between chylomicron apoA-I and HDL apoA-I. In contrast, HDL apoA-II derived from (131)I-labeled chylomicra had no early S.A. increase and began to die away immediately after injection. Labeled apoA-I from chylomicron and HDL origin had similar plasma fractional catabolic rates (FCR = 0.34-0.38 vs. 0.32-0.38 d(-1), respectively); apoA-II from chylomicron or HDL origin also had similar FCR (0.46-0.51 vs. 0.42-0.51 d(-1), respectively), which were significantly shorter than those for HDL apoA-I. There was a consistent trend toward a higher FCR for HDL apoA-I or A-II of polyunsaturated fat-fed recipients. Chylomicron apoA-I/triglyceride and apoA-II/triglyceride mass ratios were lower in polyunsaturated fat-fed animals (A-I/TG = 1.56 x 10(-3); A-II/TG = 1.47 x 10(-3)) vs. saturated fat-fed animals (A-I/TG = 2.58 x 10(-3); A-II/TG = 2.77 x 10(-3)). It was concluded that: (1) dietary polyunsaturated fat significantly lowered plasma cholesterol, HDL, and apoA-I concentrations relative to saturated fat; (2) the HDL-lowering effect of the dietary polyunsaturated fat may be due to the combined effects of decreased apoprotein production by the intestine and increased HDL catabolism; and (3) in the blood, chylomicron apoA-I and A-II differ in their metabolic fates.-Parks, J. S., and L. L. Rudel. Different kinetic fates of apolipoproteins A-I and A-II from lymph chylomicra of nonhuman primates. Effect of saturated versus polyunsaturated dietary fat.

Animals↗
PubMed1981

Physical characterization of lymph chylomicrons and very low density lipoproteins from nonhuman primates fed saturated dietary fat.

Differential scanning calorimetry (DSC) and x-ray diffraction studies were performed on chylomicrons and very low density lipoproteins (VLDL), from nonhuman primates fed saturated fat, isolated from lymph at two different temperatures (15 and 39 degrees C). When heated from -10 leads to 60 degrees C, chylomicrons and VLDL isolated at 15 degrees C had two endothermic transitions resulting from the melting of triglycerides (TG). Cooling resulted in the onset of crystallization of the TG core at 16-19 degrees C; 50% of the TG in the particles remained fluid at 4 degrees C. The initial DSC pattern was reproduced not on immediate reheating, but by storing samples at 4 degrees C overnight. Chylomicrons isolated at 39 degrees C contained a metastable (undercooled) TG core until cooled to the onset of TG crystallization at 16-19 degrees C. Reheating the particles with crystalline TG to body temperature (39 degrees C) resulted in a partially crystalline TG core, not an undercooled liquid. To ascertain the effect of particle structure on the TG physical properties, intact particles were compared with heat denatured particles and extracted lipids. The onset of crystallization was lower and the time necessary for isothermal crystallization was much greater for intact versus denatured particles or lipids. Only minor differences in physical properties as a function of particle size were found. It was concluded that: 1) the physical state of chylomicrons and VLDL TG core can be modified by isolation temperature; 2) particle structure affects crystallization but not melting of chylomicrons and VLDL TG; and 3) chylomicrons particle size does not markedly influence the physical properties of the TG core.

Animals↗
PubMed1981

Cytogenetic and endocrine findings in a female with 45,X,t(y;18) (p11;p11).

A 23-year-old phenotypic female with congenital heart disease, mental retardation and mild virilization was referred for evaluation of short stature and delayed sexual development. Endocrine studies revealed a markedly elevated serum testosterone, which was within the adult range. At laparotomy, a small uterus, normal fallopian tubes and bilateral gonadal tumors, consisting of a left gonadoblastoma and right dysgerminoma were found. Trypsin G banding of peripheral blood revealed a 45,XO, 18p+ karyotype. Q banding demonstrated intense fluorescence of the distal portion of the extra material on chromosome 18, consistent with fluorescence of Y chromosomal heterochromatin. A combination of banding techniques enabled us to determine a 45,X,t(Y;18) (p11;p11) karyotype in peripheral blood. Cultures of gonadal tissue revealed 45,X,t(Y;18)/46,XY mosaicism.

Adult↗
PubMed1981

Thyrotropin in human breast milk.

The thyrotropin (TSH) content of human breast milk was investigated, using both direct 125I-TSH radioimmunoassay and radioimmunoassay preceded by a partial purification step of elution from concanavalin A-Sepharose 4B. 15 samples of human milk between 1 and 13 weeks post-partum were found to contain 2.0 +/- (SD) 0.9 microU TSH/ml when assayed after Con A-extraction and adjusted for recovery by interpolation of a standard curve of Con A-extracted TSH standards. Recovery of 125I-hTSH tracer from both serum standards (58.6 +/- 5.5%; n = 10) and milk (53.6 +/- 6.7%; n = 15) were comparable. TSH levels obtained post-extraction were not significantly different from those that TSH is present in human breast milk in low concentrations, comparable to those normally found in the serum of euthyroid adults.

Adult↗
PubMed1980

Detection of immunological heterogeneity of an isolated, purified protein (vervet apolipoprotein A-I).

Using a single goat antiserum, we have identified immunological heterogeneity of purified apolipoprotein A-I from high density lipoprotein of vervet monkeys. We examined whether the apparent heterogeneity was due to separate antigenic sites within the polypeptide sequence or rather on the different isoproteins, which result in charge heterogeneity of this protein. The apolipoprotein A-I was cleaved with cyanogen bromide and the resulting three fragments were purified and characterized. By using immunodiffusion, each of the fragments was found to show a characteristic and different reaction to the antiserum. By contrast, apparent identity was found by immunodiffusion among the separate isoprotein forms of apolipoprotein A-I. We have concluded that the immunological heterogeneity of apolipoprotein A-I was due to different antigenic sites within the primary sequence of apolipoprotein A-I.

Amino Acids↗
PubMed1980

Thyroidal response to peroral TSH in suckling and weaned rats.

The biological activity of perorally administered bovine thyroid-stimulating hormone (bTSH) was investigated in suckling (14-day-old) and weaned (30-day-old) rats. Animals were treated with water or bTSH given either by subcutaneous injection or by the oral route. Both suckling and weaned animals responded to subcutaneous administration of bTSH by an increase in serum thyroxine (T4) and triiodothyronine (T3) concentrations. Bovine TSH administered orally to weaned animals had no effect on thyroid hormone levels. In contrast, suckling pups responded to perorally administered bTSH with increases of T4 and T3 levels comparable to those achieved in animals that received bTSH subcutaneously. The characteristics of the gastric secretion and intestinal epithelium of the weaned animal, therefore, appear to play a role in preventing absorption of a polypeptide hormone. However, protein hormones contained in maternal milk can be transferred to the suckling in which their full biological functions can be expressed.

Administration, Oral↗
PubMed1979

An outbreak of vitamin D deficiency rickets in a susceptible population.

Nutritional, racial, cultural, and environmental factors have combined to produce a resurgence of vitamin D deficiency rickets in urban Philadelphia. Between January 1974 and June 1978, 24 cases were diagnosed at the Children's Hospital of Philadelphia. Patients' ages ranged from 4 to 58 months. Presenting complaints included seizures, swollen wrists, pathologic fractures, and developmental regression. Sixteen patients were below the third percentile for length and weight. Laboratory results indicated vitamin D deficiency in nursing mothers as well as in infants. All infants had been breast-fed and all were black. Ingestion of vitamin D was limited by exclusion of meat and/or dairy products in 21, and no infants had consistently taken supplemental vitamins. Nineteen were members of Muslim or Seventh Day Adventist faiths. Endogenous synthesis of vitamin D was limited by dark skin, by dressing in long garments with hoods and veils, and by air pollution in a densely populated northern city. The return to a more "natural" diet, free of food additives, has been accompanied by the return of a classic disease of industrial society. Effective management required patience and respect for religious convictions. With treatment, there was correction of chemical and skeletal abnormalities, but few patients showed catch-up growth.

Black or African American↗