Biomedical subjects

J S Chan

Publications and source records attributed to J S Chan.

At least 55 records · Page 3Linked to original sources

PubMed1995

Regulation of multiple effectors by the cloned delta-opioid receptor: stimulation of phospholipase C and type II adenylyl cyclase.

The delta-opioid receptor is known to regulate multiple effectors in various tissues. When expressed in human embryonic kidney 293 cells, the cloned delta-opioid receptor inhibited cyclic AMP (cAMP) accumulation in response to the delta-selective agonist [D-Pen2,D-Pen5]-enkephalin. The inhibitory response of [D-Pen2,D-Pen5]-enkephalin was dependent on the expression of the delta-opioid receptor and exhibited an EC50 of 1 nM. The receptor showed ligand selectivity and a pharmacological profile that is appropriate for the delta-opioid subtype. The inhibition was blocked by the opiate antagonist naloxone or by pretreatment of the cells with pertussis toxin. Co-transfection of the delta-opioid receptor with type II adenylyl cyclase and an activated mutant of alpha s converted the delta-opioid signal from inhibition to stimulation of cAMP accumulation. It is interesting that when transfected into Ltk-fibroblasts, the cloned delta-opioid receptor was able to stimulate the formation of inositol phosphates (EC50 = 8 nM). This response was sensitive to pertussis toxin. The opioid-mediated formation of inositol phosphates exhibited the same ligand selectivity as seen with the inhibition of cAMP accumulation. The ability of the delta-opioid receptor to couple to G proteins other than Gi was also examined. Cotransfection studies revealed that the delta-opioid receptor can utilize Gz to regulate cAMP accumulation and to stimulate the formation of inositol phosphates.

Adenylyl Cyclases↗

PubMed1995

Activation of type II adenylyl cyclase by the cloned mu-opioid receptor: coupling to multiple G proteins.

Opioid receptors are multifunctional receptors that utilize G proteins for signal transduction. The cloned delta-opioid receptor has been shown recently to stimulate phospholipase C, as well as to inhibit or stimulate different isoforms of adenylyl cyclase. By using transient transfection studies, the ability of the cloned mu-opioid receptor to stimulate type II adenylyl cyclase was examined. Co-expression of the mu-opioid receptor with type II adenylyl cyclase in human embryonic kidney 293 cells allowed the mu-selective agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, to stimulate cyclic AMP accumulation in a dose-dependent manner. The opioid-induced stimulation of type II adenylyl cyclase was mediated via pertussis toxin-sensitive Gi proteins, because it was abolished completely by the toxin. Possible coupling between the mu-opioid receptor and various G protein alpha subunits was examined in the type II adenylyl cyclase system. The opioid-induced response became pertussis toxin-insensitive and was enhanced significantly upon co-expression with the alpha subunit of Gz, whereas those of Gq, G12, or G13 inhibited the opioid response. When pertussis toxin-sensitive G protein alpha subunits were tested under similar conditions, all three forms of alpha i and both forms of alpha o were able to enhance the opioid response to various extents. Enhancement of type II adenylyl cyclase responses by the co-expression of alpha subunits reflects a functional coupling between alpha subunits and the mu-opioid receptor, because such potentiations were not observed with the constitutively activated alpha subunit mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗

PubMed1995

Accuracy of videokeratography for instantaneous radius in keratoconus.

PURPOSE: Present videokeratographs provide corneal radius of curvature measurements in terms of axial (sagittal) radius and, for some instruments, instantaneous (tangential) radius. The EyeSys videokeratograph allows conversion from axial to instantaneous radius based on an algorithm, which assumes a basic corneal shape of elliptical form. METHOD: We tested the accuracy of the EyeSys instantaneous radius algorithm for 29 keratoconic corneas using the criterion that instantaneous radius of the cone apex could be determined accurately by aligning the cone apex with the optic axis of the videokeratoscope. RESULTS: There was a close relation between the instantaneous values obtained from the regular and apex alignments for the 17 eyes with cone apices below 55 D (95% limits of agreement -0.39 to 1.49 D), but not for the 12 eyes above 55 D (95% limits of agreement -4.87 to 6.61 D). The mean distance of the cone position from the center of the map was 1.16 mm for the instantaneous map and 1.59 mm for the axial map. CONCLUSION: Assuming the criterion for accuracy to be the corneal radii found when the videokeratograph was aligned with the cone apex, the instantaneous map for the EyeSys videokeratograph at regular alignment provided reasonably valid measurements for corneas up to 55 D, but large errors existed for some corneas of higher power.

Adolescent↗

PubMed1995

Expression of the angiotensinogen gene is synergistically stimulated by 8-BrcAMP and Dex in opossum kidney cells.

We transiently transfected fusion genes with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase (CAT) coding sequence as a reporter into opossum kidney (OK) cells. The addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) (10(-3)-10(-7) M) or forskolin (10(-9)-10(-5) M) stimulated the expression of the plasmid pOCAT [angiotensinogen nucleotide (N) -1498/+18] fusion gene in OK cells in a dose-dependent manner. The addition of dexamethasone (Dex) (10(-6) M) further enhanced the stimulatory effect of 8-BrcAMP or forskolin, whereas the addition of (R)-p-adenosine 3',5'-cyclic monophosphorothioate [(Rp)-cAMP[S], an inhibitor of cAMP-dependent protein kinase A, I and II] blocked the stimulatory effect of 8-BrcAMP. Furthermore, the addition of 8-BrcAMP (10(-3) M) or Dex (10(-6) M) or a combination of both stimulated the expression of pOCAT (angiotensinogen N -1138/+18), pOCAT (angiotensinogen N -960/+18), pOCAT (angiotensinogen N -814/+18), and pOCAT (angiotensinogen N -688/+18), but had no effect on the expression of pOCAT (angiotensinogen N -280/+18), pOCAT (angiotensinogen N -198/+18), pOCAT (angiotensinogen N -110/+18), pOCAT (angiotensinogen N -53/+18), and pOCAT (angiotensinogen N -35/+18). To further localize the putative cAMP-responsive element (CRE) in the angiotensinogen gene, we constructed fusion genes by inserting the DNA fragments angiotensinogen N -814 to N -689, angiotensinogen N -814 to N -761, and angiotensinogen N -760 to N -689 of the 5'-flanking region of the angiotensinogen gene upstream of the thymidine kinase (TK) promoter fused to a CAT gene and introduced them into OK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Beta-adrenergic receptors and angiotensinogen gene expression in mouse hepatoma cells in vitro.

We have previously reported that addition of 8-bromocyclic AMP enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells in vitro. Isoproterenol is known to stimulate the synthesis of hepatic intracellular cyclic AMP via beta-adrenergic receptors. To study the possible effect of beta-adrenergic receptors on the expression of the angiotensinogen gene in mouse hepatoma cells, we transiently transfected them with a fusion gene with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase coding sequence as a reporter, pOCAT (ANG N-1498/+18). The addition of isoproterenol (10(-9) to 10(-5) mol/L) alone had no stimulatory effect on the expression of pOCAT (ANG N-1498/+18). In the presence of dexamethasone (10(-6) mol/L), however, isoproterenol enhanced the stimulatory effect on the dexamethasone on the expression of pOCAT (ANG N-1498/+18). The enhancing effect of isoproterenol was inhibited by the presence of propranolol (beta 1- and beta 2-adrenergic receptor antagonist) and ICI 118,551 (beta 2-adrenergic receptor antagonist) but not by the presence of atenolol (beta 1-adrenergic receptor antagonist). Furthermore, the addition of Rp-cAMP (an inhibitor of protein kinase A I and II) blocked the enhancing effect of isoproterenol. These studies demonstrated that isoproterenol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via beta 2-adrenergic receptor and cyclic AMP-dependent protein kinase pathways. Our data may be important in understanding the molecular mechanism(s) of the stimulatory effect of catecholamines/glucocorticoid-induced expression of the angiotensinogen gene in the liver.

Angiotensin II↗

PubMed1995

Predictors of postnatal head molding in very low birth weight infants.

This study examined potential predictors of postnatal head molding in very low birth weight (VLBW) infants. Occipital-frontal circumference (OFC) and anterior-posterior (AP) and biparietal (BP) diameter measurements were obtained on 144 premature infants with birth weights of less than 1,500 gm. Measurements were obtained at four days of age (baseline) and weekly until discharge. Increasing gestational age, higher birth weight, and delivery by cesarean section predicted larger OFC at three weeks of life. Only baseline AP:BP measurements significantly predicted AP:BP measurements at week 3 and 5. Within-group t-tests indicated that the severity of head molding (as indicated by AP:BP ratio) increased throughout the first six weeks of life. Results indicate that postnatal head molding can be reliably predicted and that neonates with higher AP:BP ratios at birth are at greater risk for continued narrow, elongated head shape.

Cephalometry↗

PubMed1994

Isoproterenol and 8-bromo-cyclic adenosine monophosphate stimulate the expression of the angiotensinogen gene in opossum kidney cells.

To investigate whether the expression of the renal angiotensinogen (ANG) gene is regulated by beta-adrenoceptors and the cAMP-dependent protein kinase A pathway, we introduced stably the fusion gene containing the 5'-flanking regulatory sequence of the ANG gene with a human growth hormone (hGH) gene as a reporter, pOGH (ANG N-1498/+18), into opossum kidney (OK) cells. We successfully obtained several stable transformants with a high expression of the pOGH (ANG N-1498/+18) fusion gene. One stable transformant (OK 27) that is able to maintain the expression of pOGH (ANG N-1498/+18) in culture for more than a year was used in the present study. The level of expression of the pOGH (ANG N-1498/+18) in OK 27 was evaluated by the amount of immunoreactive-hGH (IR-hGH) secreted into the culture medium. The addition of isoproterenol (10(-11) M to 10(-9) M) stimulated the expression of pOGH (ANG N-1498/+18) and increased the accumulation of intracellular cAMP. Higher concentrations of isoproterenol (that is, greater than 10(-9) M) had low or minimal effect. In contrast, the addition of 8-bromo-cAMP (8-Br-cAMP) and forskolin stimulated the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner. The stimulatory effect of isoproterenol was blocked by the presence of propranolol, atenolol and ICI 118,551. The addition of ICI 118,551, however, was less effective than atenolol. Furthermore, the stimulatory effect of isoproterenol and 8-Br-cAMP on the expression of the pOGH (ANG N-1498/+18) was inhibited by the presence of Rp-cAMP (an inhibitor of cAMP-dependent protein kinase A I and II).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

Hormonal regulation of expression of the angiotensinogen gene in cultured mouse hepatoma cells.

To investigate the hormonal regulation of expression of the angiotensinogen (ANG) gene in the liver, we constructed fusion genes with various lengths of the 5'-flanking region of the rat ANG gene linked to a bacterial chloramphenicol acetyl transferase (CAT) gene as reporter and introduced them into mouse hepatoma cells (Hepa 1-6). As a negative control, we introduced them into a nonhepatic cell line, a mouse testicular Sertoli (TM4) cell line. The level of expression of ANG-CAT fusion genes, pOCAT (ANG N-1498/+18), pOCAT (ANG N-688/+18), pOCAT (ANG N-110/+18), pOCAT (ANG N-53/+18) and (ANG-35/+18) were 3.7, 4, 1.1, 4, and 3-fold higher than promoterless pOCAT in Hepa 1-6 cells. No significant expression of any of these ANG-CAT fusion genes over the promoterless pOCAT was observed in Sertoli TM4 cells. The addition of dexamethasone (10(-10) to 10(-4) mol/L) stimulated the expression of the pOCAT (ANG N-1498/+18) fusion gene in Hepa 1-6 cells in a dose-dependent manner with a maximum stimulation at 10(-4) mol/L and a half-maximal stimulation at 10(-8) mol/L. A combination of dexamethasone (10(-6) mol/L) and 8-bromo-cyclic AMP (cAMP) (10(-3) mol/L) further enhanced the effect of the dexamethasone alone although cAMP alone had no effect. Testosterone (10(-6) mol/L), estradiol (10(-6) mol/L), progesterone (10(-6) mol/L), and thyroid hormone (L-T3, 10(-6) mol/L) did not have this effect in either the presence or absence of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

PubMed1993

Communicating the financial worth of the CNS through the use of fiscal reports.

To maintain the clinical nurse specialist's (CNS's) leading role within hospital nursing services, routine communication to hospital administration of the impact of the CNS role on the hospital's budget is imperative. The CNS group at Children's Hospital of The King's Daughters implemented a quarterly Fiscal Report to clarify the financial worth of CNS practice. The Fiscal Report presents cost savings and revenue generating activities utilizing the role components of the CNS. During fiscal year 1991, the CNS group reported a total impact of $1,600,000. This article describes in detail the use of the Fiscal Report.

Budgets↗

PubMed1993

The effects of a pressure relief mattress on postnatal head molding in very low birth weight infants.

Very low birth weight (VLBW) infants often develop postnatal head molding (PHM)--an elongation of the skull--when a standard, firm mattress is used. This study was undertaken to determine if a pressure relief mattress (PRM) might reduce the severity of PHM. One hundred twenty-eight infants (birth weight range 567-1,490 gm, mean 1,084; gestational age range 24-36 weeks, mean 28.5) with no congenital or acquired anomalies affecting head growth were randomly assigned to a control group (standard, firm mattress) or a study group (PRM). Study infants were placed on the PRM within 72 hours of birth. Occipitofrontal circumference (OFC) and anterior-posterior (AP) and biparietal (BP) diameters were measured at day four, seven, and then at one week intervals of life until the infant reached 2,000 gm or was discharged. An electronic digital caliper with an accuracy of 0.025 mm was used to obtain the AP and BP measurements. T-tests revealed no significant differences in head shape between the two groups. In conclusion, the pressure relief mattress did not reduce PHM in VLBW infants.

Bedding and Linens↗

PubMed1992

Hormonal regulation of expression of the angiotensinogen gene in cultured opossum kidney proximal tubular cells.

Angiotensinogen (ANG) messenger RNA is expressed in cultured opossum kidney (OK) proximal tubular cells. The aim of these studies was to investigate whether steroid hormones (dexamethasone, estradiol, testosterone, and progesterone) could stimulate the expression of renal ANG gene in vitro. Fusion genes consisting of various lengths of the 5'-flanking region of the rat ANG gene linked to a chloramphenicol acetyl transferase (CAT) reporter gene were constructed and introduced into cultured OK cells. The level of expression of fusion genes was determined by the level of cellular CAT enzymatic activity. The addition of dexamethasone (10(-12) to 10(-6) M) stimulates the expression of the pOCAT (ANG N-1498/+18) fusion gene in OK cells in a dose-dependent manner with a maximum stimulation at 10(-6) M and a half-maximal stimulation at 10(-9) M. Combination of dexamethasone (10(-6) M) and thyroid hormone, L-T3 (10(-6) M), further enhanced the effect of the dexamethasone alone. Testosterone (10(-6) M), estradiol (10(-6) M), and progesterone (10(-6) M) did not have this effect. Moreover, dexamethasone also stimulates the expression of the pOCAT (ANG N-688/+18) but not pOCAT (ANG N-110/+18), pOCAT (ANG N-53/+18) and pOCAT (ANG N-35/+18). These studies demonstrate that the glucocorticoid hormone is effective at stimulating the transcription of the ANG gene in OK cells, but stimulation is not observed from testosterone, estradiol, or progesterone. Moreover, glucocorticoid and L-T3 act synergistically to stimulate the transcription of the ANG gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1992

Thyroid hormone, L-T3, stimulates the expression of the angiotensinogen gene in cultured opossum kidney (OK) cells.

Angiotensinogen (ANG) messenger RNA is expressed in opossum kidney (OK) proximal tubular cells. To examine whether thyroid hormone, L-T3, could stimulate the expression of the ANG gene in OK proximal tubular cells, fusion genes, consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone reporter gene, were constructed and introduced into OK cells. As a negative control, they were introduced into a nonkidney cell line, a human choriocarcinoma cell line (JEG-3). The level of the expression of fusion genes in these cells were determined by the level of immunoreactive human growth hormone secreted into the culture medium. The expression of ANG-growth hormone (ANG-GH) fusion genes pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 226-, 4.5-, 1.0-, 12-, and 2.5-fold higher than promoterless pOGH in the expression of growth hormone activity in OK cells. No significant expression of any of these ANG-GH fusion genes over the promoterless pOGH was observed in JEG-3 cells. The addition of L-T3 stimulates the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner with a maximal and half-maximal effect at 10(-7) M and at 10(-8) to 10(-9) M, respectively. Thyroid hormone (10(-7) M) also stimulates the expression of pOGH (ANG N-688/+18) but not pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), or pOGH (ANG N-35/+18).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1990

Molecular cloning and expression of the rat angiotensinogen gene.

To identify tissue- and hormonal-specific DNA control cis-elements in the rat gene, we have constructed fusion genes consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone (hGH) reporter gene and have introduced them into a subclone of rat pancreatic islet tumor cell line (1056A) which expresses the highest level of angiotensinogen mRNA. As a negative control, we have also introduced them into a human choriocarcinoma cell line (JEG-3), which does not express the endogenous angiotensinogen gene. The level of the expression of these fusion genes in these cells was determined by the level of immunoreactive hGH secreted into the culture medium. The expression of angiotensinogen-growth hormone (ANG-GH) fusion genes, pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 1.0, 1.8, 1.5, 12.0 and 3.0-fold higher, respectively, than the promoterless growth hormone expression vector (pOGH). The addition of dexamethasone (10(-6) M), aldosterone (10(-5) M), and thyroid hormone, L-T3 (10(-7) M), stimulated the expression of pOGH (ANG N-1498/+18) by 4.0-, 2.5-, and 2.0-fold above the control level, respectively. Combination of dexamethasone (10(-6) M), L-T3 (10(-7) M), and ethinyl-estradiol (10(-6) M) stimulated the expression of the pOGH (ANG N-1498/+18) to greater than 10-fold over the control. Ethinyl-estradiol (10(-6) M) or progesterone (10(-6) M) alone had no effect on the expression of the pOGH (ANG N-1498/+18).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1989

Somatostatin gene expression in pancreatic islet cells is directed by cell-specific DNA control elements and DNA-binding proteins.

Somatostatin is a peptide synthesized in the pancreatic islets, nervous system, gastrointestinal tract, and thyroid gland. Factors that control islet cell-specific expression of the somatostatin gene were analyzed by expression of fusion genes consisting of 5' rat somatostatin gene sequences linked to coding sequences of the receptor genes, bacterial chloramphenicol acetyltransferase, and human growth hormone. Fusion genes containing 900 and 250 base pairs (bp) of 5'-flanking DNA were preferentially expressed at 5-10-fold higher levels in somatostatin-producing islet cell lines, as compared with islet cell lines that produced insulin and glucagon, and in three non-islet cell lines. A deletional mutation consisting of only 65 bp of 5'-flanking sequence of the rat somatostatin gene expressed in all islet cell lines but not in non-islet lines, indicating the existence of a negative-acting islet cell-specific element located between nucleotides -250 and -65. The 65-bp sequence contains the octameric cAMP-responsive enhancer (CRE) TGACGTCA (nucleotides -48 to -41). Fine mapping of sequences responsible for islet-specific expression by substitution of synthetic oligonucleotide cassettes revealed full retention of expression by deletion to nucleotides -48 and complete loss of expression at nucleotides -42 of the CRE. Substitution of the 9 bp adjacent 3' to the CRE of the somatostatin gene (nucleotides -40 to -32) with the corresponding sequence located 3' to the CRE of the glucagon gene abolished expression. By gel mobility shift and DNaseI footprinting analyses, proteins in extracts of islet cells bound to the 24 bp including the CRE and downstream adjacent 9 bp (nucleotides -58 to -35). An additional upstream region of DNA was protected from DNase I digestion (nucleotides -110 to -80). Proteins from non-islet cells bound to the region from nucleotides -58 to -35, but patterns of DNase I protection differed from those using proteins from islet cells. These observations indicate that several DNA-binding proteins interact with cis-acting elements located between 35 and 58 bp upstream of the transcriptional start site of the rat somatostatin gene to determine islet cell-specific gene expression. CRE-binding protein(s) is ubiquitous among phenotypically different cells, and expression of the somatostatin gene in non-somatostatin-producing islet cells appears to be inhibited by a negative-acting element located upstream of the CRE.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1989

Urinary levels of immunoreactive NH2-terminal of pro-opiomelanocortin in patients with malignant pulmonary disease.

Urinary levels of immunoreactive (IR) human NH2-terminal (hNT) of pro-opiomelanocortin were measured in 43 patients with various cell types of lung cancer (19 squamous cells, 12 oat cells, 2 large cells, and 10 adenocarcinoma), 32 patients with benign lung disease, two patients after hypophysectomy, and in 23 healthy volunteers. Lung cancer patients were divided into two subgroups according to the stage of the disease: 22 patients had "limited", and 21 patients "extensive" disease. Urinary and plasma levels were measured in 9 patients with lung cancer before and after radio- and chemotherapy or surgery. Urine samples were dialyzed and IR hNT material was extracted by Sep Pak C-18 cartridges using a propanol-2/TFA solvent system. The plasma and urinary IR hNT levels of the normal controls were 124 +/- 25 pg/ml and 47.8 +/- 14.5 pg/mg creatinine, respectively. The plasma levels of IR hNT were elevated (greater than mean + 2SD) in 65% of our patients with histologically proven lung cancer (422 +/- 775, mean +/- SD, pg/ml). The highest incidence of an elevated plasma level of IR hNT was found in oat cell carcinoma (83%). Elevated plasma IR hNT occurred in 66% of the patients with benign pulmonary disease (246 +/- 141 pg/ml, N.S.). In cancer patients with "limited" disease we found levels of 226 +/- 143 pg/ml and in patients with "extensive" disease 627 +/- 1074 pg/ml (N.S.). The urinary IR hNT level in lung cancer patients was 186 +/- 337 pg/mg creatinine and 81% of our patients had elevated levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Peptides related to the N-terminus of pro-opiomelanocortin in the human adrenal medulla.

The immunoreactive (IR) human N-terminal (hNT) of pro-opiomelanocortin (POMC) was measured by specific radioimmunoassay (RIA) and characterized by molecular sieving chromatography, concanavalin A-affinity chromatography and reversed-phase high-performance liquid chromatography (HPLC). The IR hNT levels were 380 +/- 144 ng/g wet wt (mean +/- SD) in the adrenal medulla (N:6), 21.6 +/- 6 ng/g wet wt in the adrenal cortex (N:6), and 45.6% ng/g wet wt in pheochromocytoma tissues (N:3). The IR hNT content of the adrenal medulla was found to be at least twice as high as that of the IR ACTH on a molar basis. Molecular sieving chromatography of IR hNT and IR gamma-3-melanotropin (MSH) showed two major molecular forms (apparent molecular weights of 14 and 12 kilodalton). These major forms were also separable using reversed-phase HPLC. In addition, a part of the IR ACTH material from the adrenal medulla extracts was eluted with an apparent molecular weight of 12 kilodalton. This latter form of IR ACTH was also separated from authentic human ACTH (1-39) by HPLC. Results obtained from concanavalin A-agarose chromatography suggest that one part of the IR gamma-3-MSH material from the adrenal medulla might be non-glycosylated. These results indicate the presence of IR hNT and IR gamma-3-MSH-like material in the human adrenal and also suggest a different processing pathway for POMC from that in the pituitary gland.

Adrenal Cortex↗

PubMed1989

Value of plasma NH2-terminal fragment of pro-opiomelanocortin in marking human lung cancer in various clinical settings.

Plasma concentration of amino-terminal segment of pro-opiomelanocortin (N-POMC) was measured by radioimmunoassay (RIA) in 144 patients with various forms of lung cancer during pneumonectomy, at different times of the day after being newly diagnosed and serially, throughout their treatment (surgery or chemotherapy) in order to assess its value as a biomarker in this disease. Normal volunteers, coal miners smoking but without known lung diseases, and the patients with diverse pulmonary disorders served as comparison groups. A significant transtumoral gradient of N-POMC was found at surgery in 15 of 57 (26%) patients. Subjects without lung afflictions had significantly lower N-POMC levels than patients with pulmonary diseases (benign or malignant) only when the blood was drawn before breakfast. Furthermore, fasting levels in all subgroups of patients were higher at any time of the day than nonfasting ones. Finally, N-POMC levels did not decrease significantly after successful treatment of lung cancer (by surgery or chemotherapy) but were markedly higher after relapse. These results suggest that N-POMC, despite the fact that it cannot be used to discriminate lung cancer patients from controls, is a biomarker which may predict relapse in patients successfully treated by chemotherapy for their pulmonary neoplasm.

Adult↗

PubMed1988

Cytologic criteria for fibroadenoma. A step-wise logistic regression analysis.

The authors reviewed the fine-needle aspiration biopsy smears from 62 subjects with proven fibroadenoma, 60 subjects with proven ductal carcinoma, and 42 subjects with proven fibrocystic disease. All smears were coded as to the presence or absence of the following variables: epithelial cells, stroma, honeycomb sheets, antler horn clusters, naked nuclei, nucleoli, marked cellularity, foam cells, apocrine cells, anisokaryosis, atypical nuclear hyperchromasia, single cells with cytoplasm, mitotic figures, and nuclei greater than two red blood cell diameters. Step-wise logistic regression analyses were performed to determine the variables predictive of fibroadenoma. The statistical analyses selected stroma, antler horn clusters, and marked cellularity as the key cytologic criteria to differentiate fibroadenomas from fibrocystic disease. The statistical analyses selected stroma, antler horn clusters, and honeycomb sheets as the key cytologic criteria to differentiate fibroadenoma from ductal carcinoma.

Adenofibroma↗