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Biomedical subjects

E Chin

Publications and source records attributed to E Chin.

At least 55 records · Page 3Linked to original sources
PubMed1993

Significant species differences in local IGF-I and -II gene expression.

Comparison of renal and ovarian IGF system gene expression in the rat and human has shown that IGF-I mRNA is predominant in rat and IGF-II in human tissues, and that the two IGFs demonstrate different cellular patterns of expression in the homologous organs. IGF-I receptor gene expression, however, describes an apparently identical pattern in the tissues of both rat and human, suggesting that, although local sources and presumably regulation of IGF expression vary between the species, the ultimate functions served might be the same.

Animals↗
PubMed1993

Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney.

In situ hybridization was used to map cellular patterns of gene expression for facilitative glucose transporters (GTs) 1-5 in the developing and adult rat kidney. GT3 was not detected. GT1 mRNA was present in the proximal straight tubule (PST), distal nephron and collecting duct. GT2 mRNA was localized in both proximal convoluted and PST, while GT5 mRNA was detected only in the PST. GT4 mRNA and immunoreactivity were focally localized in the thick ascending limb of Henle's loop and were coexpressed with IGF-I. Thus, each of the four different isoforms demonstrated a distinct renal distribution, with GTs 1, 2, and 5 coexpressed in the PST. Renal GT1 and GT5 gene expression were unchanged throughout development, while GT2 was most abundant before weaning and GT4 was first detected after weaning. Only GT4 appeared to be hormonally regulated: It was decreased after hypophysectomy and increased after vasopressin treatment, but was not affected by 1 or 4 d of insulinopenic diabetes mellitus. The coexpression of GT4 and IGF-I in the thick ascending limb segment of the nephron suggests a novel autocrine/paracrine mechanism by which cells may control local fuel economy independently from that of the larger structure to which they belong and from the systemic hormonal milieu.

Animals↗
PubMed1993

Insulin receptor-related receptor messenger ribonucleic acid is focally expressed in sympathetic and sensory neurons and renal distal tubule cells.

The insulin receptor-related receptor (IRR) demonstrates striking structural homology to the insulin receptor (IR) and insulin-like growth factor-I receptor (IGFR), suggesting that IRR is a member of the IR family. However, the endogenous ligand and biological role for this "orphan" receptor are unknown. To identify potential sites of action for the IRR, in situ hybridization was employed to reveal cellular patterns of IRR gene expression in the developing and adult rat and in the adult human kidney. From embryonic days 15-20, IRR mRNA is most abundant in sensory neurons of the trigeminal and dorsal root ganglia and, to a lesser extent, neurons of the autonomic system. IRR gene expression diminishes in the majority of sensory neurons postnatally, but remains abundant in a subpopulation of adult rat trigeminal and dorsal root ganglion neurons. IRR mRNA is localized in peripheral autonomic ganglia localized in the adrenal medulla and renal hilum in the adult. From birth to maturity, IRR mRNA is abundant in renal epithelial cells focally localized in the distal tubule in both rat and human kidney. The specificity of this pattern of IRR gene expression was demonstrated by hybridization of serial tissue sections with two different nonoverlapping cRNA probes. Nonspecific signal, as measured by IRR sense probe hybridization, was negligible. This highly restricted pattern of IRR gene expression is in marked contrast to the very widespread pattern of gene expression demonstrated by the IR and IGFR. This study showed that IRR, IR, and IGFR mRNAs were colocalized in some sensory neurons, suggesting the possibility for hybrid receptor formation in these cells. In summary, IRR gene expression is focally localized in sensory and autonomic neurons and renal distal tubule cells. These observations suggest that the IRR, in contrast to the related IR and IGFR, serves a narrow cell-specific role.

Animals↗
PubMed1992

Anatomical relationships in the patterns of insulin-like growth factor (IGF)-I, IGF binding protein-1, and IGF-I receptor gene expression in the rat kidney.

The rat kidney is both a target of circulating insulin-like growth factor-I (IGF-I) and a site of local IGF-I production. In order to identify which renal structures produce IGF-I and the functionally related IGF binding protein 1 (IGFBP-1), and which structures are potential sites of circulating or endogenous renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP-1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF-I receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are both localized in the epithelial cells of medullary thick ascending limbs (TALs) of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant in TALs, but, in addition, is distributed throughout the distal nephron and collecting duct, and in the glomerulus, with lowest levels found in proximal tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I receptor mRNA levels were not significantly effected by either treatment. However, the most dramatic effect produced by the interruption of the pituitary-renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene expression in individual kidneys and even in individual nephrons, suggesting a local interaction between IGF-I and IGFBP-1 in the regulation of their respective mRNA levels. Functional implications issuing from these anatomical relationships in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP-1, may act on luminal TAL and downstream receptor sites. The specific physiological role of IGF-I produced in TALs is open to speculation. Glomerular IGF-I receptor sites, based on their localization upstream and distant from local sources of IGF-I production, are predicted to be targets for circulating IGFs.

Aging↗
PubMed1992

Renal growth hormone receptor gene expression: relationship to renal insulin-like growth factor system.

In order to elucidate potential sites of direct GH action on the kidney, we used in situ hybridization to localize GH receptor (GHR) gene expression during the course of development and in the adult rat. In order to illuminate potential interactions between GH and insulin-like growth factor-I (IGF-I) in regulating renal function, we compared the anatomical localization of GHR messenger RNA (mRNA) with that for the IGF-I receptor and for IGF-I in the rat kidney. Low levels of GHR mRNA were present in the kidney from before birth and increased in abundance until postnatal day 40. Hypophysectomy resulted in a decrease and GH treatment resulted in an increase in renal GHR mRNA levels. Renal GHR mRNA was most abundant in the proximal straight tubule, with lesser levels present in the medullary thick ascending limb (MTAL), and it was not detected in the glomerulus or inner medulla. In contrast, IGF-I receptor mRNA was concentrated in the glomerulus, distal nephron and collecting system. The only point of convergence for GHR and IGF-I receptor mRNAs was in the MTAL, where IGF-I mRNA was localized. This segregation of GHR and IGF-I receptor gene expression in the kidney suggests that each hormone has distinct spheres of action along the nephron, with GH acting directly on the proximal straight tubule, whereas IGF-I may act on the glomerulus, distal nephron, and collecting duct. GHR expression in the MTAL, which is the site of renal IGF-I synthesis, supports the view that GH has a direct effect on renal IGF-I synthesis. Finally, it appears that in the kidney, as in other GH-sensitive tissues, GH may regulate its receptor levels.

Animals↗
PubMed1992

Insulin-like growth factor system gene expression in the human kidney.

Insulin-like growth factors (IGFs) have significant effects on renal function and have been implicated in renal development and hypertrophy. In order to investigate the renal IGF system in the human, we have used in situ hybridization to map the patterns of gene expression for IGF-I, IGF-II, IGF binding proteins-1 and -2 and both the type-I and type-II IGF receptors in the adult kidney. Since the rat is a model for the study of IGFs in renal physiology and pathophysiology, we compared patterns of IGF gene expression in the rat and human kidney. IGF-I messenger RNA (mRNA) is not detected in the human but is abundant in the rat kidney, while IGF-II is abundant in the human but not detected in the adult rat kidney. IGF-II mRNA is concentrated in renal vascular system, including afferent arterioles and the medullary interstitium. IGF-I and IGF binding protein-1 mRNAs are colocalized in the rat medullary thick ascending limbs of Henle's loops, but neither is detected in the human kidney. IGF binding protein-2 mRNA is concentrated in glomeruli in both species, but, whereas in the human it is expressed in the epithelium of the distal nephron and collecting ducts, in the rat it is localized in the medullary interstitium. The patterns for both type-I and type-II IGF receptor gene expression are identical in both species; however, type-I receptor, mRNA is distinctly more abundant than type-II. Both IGF receptor mRNAs are abundant in the renal tubular epithelium of the medulla and both are barely detectable in proximal tubules. Type I receptor mRNA alone is abundant in glomerular structures. These observations suggest that the autocrine/paracrine roles of IGFs are quite different in rat and human kidney. The conserved patterns of IGF receptor expression, however, suggests that the role of circulating IGFs in regulating renal function may be similar across the species.

Adult↗
PubMed1991

The rheumatoid factor reactivity of a human IgG monoclonal autoantibody is encoded by a variant V kappa II L chain gene.

To determine the genetic and molecular basis for rheumatoid factor (RF) autoantibody reactivity in patients with destructive, erosive arthritis, we established a human lymphoblastoid cell line (hRF-1) from a patient with polyarthritis that produced an IgG RF mAb, mAb hRF-1. Studies of isolated H and L chains showed that the specificity of RF reactivity is conferred by mAb hRF-1 L chains. The L chain gene was cloned from a cDNA library prepared from hRF-1 cells. The nucleotide sequence was similar to known V kappa II L chains except for a two nucleotide change corresponding to a change of two amino acids in an invariable region of FR3. A germ-line gene with one of the nucleotide changes was identified by polymerase chain reaction in multiple cell lines, including K562 that does not rearrange Ig genes, but the other nucleotide change appeared to be due to mutation. Either or both of these amino acid changes may contribute to the RF reactivity, because an antibody with the same V kappa II L chain except for these two amino acid changes in FR3 did not have RF reactivity. The RF reactivity of isolated L chains from mAb hRF-1 was confirmed by transfecting COS cells with an expression vector encoding the hRF-1 kappa-chain and showing that the secreted k-chains had RF reactivity. Expression of this variant V kappa II L chain gene may form the basis for RF autoantibody reactivity in some patients.

Amino Acid Sequence↗
PubMed1991

Regulation of HTLV-II gene expression by Rex involves positive and negative cis-acting elements in the 5'long terminal repeat.

Regulation of human T-cell leukemia virus type II (HTLV-II) gene expression by the trans-acting viral protein, Rex, is mediated through specific cis-acting sequences in the HTLV-II long terminal repeat (LTR). Augmentation of 5' LTR-linked gene expression by Rex requires two distinct cis-acting elements: one termed the "Rex-responsive element" (RxRE), which allows Rex to overcome the inhibitory effect of a second, termed the "cis-acting repressive sequences" (CRS). The HTLV-II RxRE is located between nt +91 and +317 relative to the cap site in the R/U5 region of the 5'LTR, and the HTLV-II CRS is contained within the RxRE from nt +208 to +317, which is downstream of the splice donor site, in the R/U5 region of the 5' LTR. Deletion of the CRS results in significantly increased cytoplasmic levels of LTR-linked mRNA independent of the presence of Rex. Our results show that Rex acts post-transcriptionally and induces a shift from nucleus to cytoplasm of gag/pol mRNA, the only HTLV-II mRNA that contains both the RxRE and the CRS in the 5' LTR-derived leader sequence.

Base Sequence↗
PubMed1991

Cellular pattern of insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the developing and mature ovarian follicle.

We have employed in situ hybridization histochemistry to map the cellular pattern of insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in developing rat ovaries from the time of birth through adulthood, and in response to hypophysectomy and gonadotropin replacement. From the early postnatal period, both IGF-I and IGF-I receptor messenger RNAs (mRNAs) were highly abundant and evenly distributed in granulosa cells of small, growing follicles. In large follicles, however, IGF-I gene expression was heterogeneous. IGF-I mRNA was most abundant in granulosa cells lining the antrum and surrounding the oocyte, but was low or undetectable in mural granulosa cells of Graafian follicles, and was also undetectable in luteinized granulosa cells of corpora lutea. IGF-I receptor mRNA was evenly distributed in developing and mature follicles and was highly abundant in the luteinized granulosa cells of corpora lutea. IGF-I receptor but not IGF-I mRNA was detected in growing oocytes. Hypophysectomy resulted in a decrease and treatment with PMSG resulted in an increase in follicular IGF-I receptor mRNA levels, whereas there was no change in IGF-I mRNA levels in the same protocol. In summary, high levels of both IGF-I and IGF-I receptor gene expression occur in the granulosa cells of actively growing follicles, suggesting that granulosa cell IGF-I may have a role in follicular or oocyte growth. IGF-I gene expression is lost concomitant with follicular enlargement and granulosa cell differentiation, whereas IGF-I receptor gene expression continues at high levels in luteinized granulosa cells, suggesting that IGF effects on differentiated granulosa cell function are due to circulating, not local, hormone. Finally, granulosa cell IGF-I receptor gene expression appears to be regulated by the gonadotropin present in pregnant mare serum.

Animals↗
PubMed1990

A clinical, hematologic, and immunologic analysis of 21 HTLV-II-infected intravenous drug users.

Infection with human T-cell leukemia virus type II (HTLV-II) has been associated with rare chronic T-cell malignancies and has recently been demonstrated in a significant proportion of American intravenous drug abusers (IVDA). Identification of an HTLV-II-infected cohort of IVDA has allowed analysis of the HTLV-II carrier state. We analyzed clinical, hematologic, and immunologic parameters in 21 HTLV-II-infected IVDA, two HTLV-I-infected IVDA, and 20 uninfected control IVDA identified by serologic screening and by analysis of peripheral blood mononuclear cell (PBMC) DNA by polymerase chain reaction (PCR). An elevated absolute lymphocyte count was observed in 4 of 21 HTLV-II-infected IVDA, 1 of 2 HTLV-I-infected IVDA, and 1 of 20 control IVDA. CD8+ T-cell elevation was observed in three of four HTLV-II IVDA with lymphocytosis and one of two HTLV-I-infected IVDA. Activation of CD8+ T cells in HTLV-II-infected IVDA was suggested by an overall increase in CD8+/HLA-DR+ lymphocytes. Cell fractionation and analysis by PCR of HTLV-II-infected carrier blood showed high levels of HTLV-II provirus in unfractionated PBMC and purified T cells and little or no detectable HTLV-II DNA in B cells or monocytes, indicating that T cells were the most likely target of infection in vivo. The frequency of HTLV-II-infected cells was estimated at approximately 1 in 500 cells or less using dilution analysis by PCR of PBMC DNA. Most HTLV-II-infected IVDA are asymptomatic and have no overt hematologic or immunologic abnormalities, although some manifest benign lymphocytosis.

Adult↗
PubMed1989

Detection of human T-cell leukemia/lymphoma virus type I in a transfusion recipient with chronic myelopathy.

A white man with a progressive spastic paraparesis that began 15 months after sustaining severe trauma in a motor vehicle accident was positive for antibodies to human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunosorbent assay. Serum antibody to HTLV-I was confirmed by Western blot and radioimmunoprecipitation assay. We detected specific proviral DNA in peripheral blood lymphocytes by the polymerase chain reaction. Because the incidence of HTLV-I is generally restricted to Southern Japan and Caribbean black populations, the most likely source of HTLV-I infection in this patient was multiple intraoperative blood transfusions. The relatively short interval between transfusion and development of HTLV-I-associated myelopathy is consistent with the more rapid evolution of this clinical syndrome compared with adult T-cell leukemia.

Chronic Disease↗
PubMed1985

Synthesis and antifertility activity of zoapatanol analogues.

The synthesis of and guinea pig contragestational screening data for several oxepane and 3,8-dioxabicyclo[3.2.1]octane analogues of zoapatanol (1) are described and their structure-activity relationships discussed. Conversion of the 5-keto group on the nonenyl side chain of 1 into a hydroxyl function enhanced the potency. Further significant enhancement in the potency was realized with the transformation of several oxepanes into the 3,8-dioxabicyclo-[3.2.1]octane-1-acetic acid derivatives. Detailed, comparative contragestational evaluation of the three most potent compounds 9, 33, and 37 is presented, which led to the selection of 33 (ORF 13811) for further biological evaluation.

Abortifacient Agents↗
PubMed1984

The significance of nonstress test from 24 to 42 weeks' gestation.

On 811 pregnant subjects, a sampling that included high-risk pregnancies, NST was performed 3,015 times from 24 to 42 weeks' gestation. Reactive NST and nonreactive NST accounted for 67.9% and 26.1%, respectively. Both amplitude and duration of acceleration showed an increase with the advance of pregnancy. The number of accelerations which occurred in the examination period increased as well. V-shaped decelerations were sometimes found in the NST recordings of normal fetuses accompanied by fetal movements, but the incidence of this type of deceleration tended to decrease as the subjects reached full term. No correlation was found between the occurrence of V-shaped deceleration during antepartum NST and that of variable deceleration during intrapartum monitoring. Taking 10 bpm and 10 seconds as the standard values of the acceleration amplitude and the duration of acceleration, respectively, there was found a significantly higher incidence of late deceleration during labor in the fetuses who showed nonreactive NST antepartally than those showed reactive NST. The incidence of persistent late deceleration was significantly higher in the nonreactive fetuses under the 10 bpm/10 second criteria than in those under the conventional 15 bpm/15 second criteria.

Female↗