Biomedical subjects

M Mercado

Publications and source records attributed to M Mercado.

13 recordsLinked to original sources

PubMed1992

Low plasma growth hormone binding protein in IDDM.

Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance is unknown; it may involve a defect at the level of the GH receptor, unresponsiveness due to a postreceptor defect in GH action, or both. To investigate a potential receptor involvement, we measured plasma high-affinity GH-binding protein (GHBP), which represents a truncated GH receptor and may reflect GH receptor levels in tissues, in patients with IDDM, patients with non-insulin-dependent diabetes (NIDDM), and nondiabetic control subjects. Patients with IDDM had significantly lower plasma GHBP levels than either patients with NIDDM or nondiabetic control subjects (mean value 18.2 vs. 24.6 and 23.8% GH bound/ml plasma, respectively, P less than 0.001). This difference persisted when only lean patients (less than 115% ideal body wt) were included in the analysis. Basal plasma GH levels were significantly elevated in IDDM compared with either patients with NIDDM or nondiabetic control subjects (mean 6.9 vs. 2.1 and 2.0 micrograms/L, respectively, P less than 0.001), whereas IFG-I levels were not significantly different in IDDM and NIDDM. No correlations were found between levels of GHBP and HbA1, duration of diabetes, or plasma GH. GHBP and IGF-I levels were significantly correlated in NIDDM but not in IDDM. We conclude that IDDM is associated with low GHBP levels and that GH resistance found in this disorder may be mediated, at least in part, by a decrease in GH receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Successful treatment of steroid-resistant double-lung allograft rejection with Orthoclone OKT3.

An 18-yr-old woman with cystic fibrosis who received a double-lung transplant developed a severe episode of acute lung rejection. Bronchoalveolar lavage and transbronchial biopsy were used to establish the diagnosis. The rejection was refractory to administration of high-dose pulse steroids. OKT3 therapy was successfully used to reverse this episode. This is the first case report of a steroid-resistant double-lung allograft rejection successfully treated with OKT3.

Adolescent↗

PubMed1990

Clinical experience with preterm formulas in very low birthweight infants.

Infants below 1500 g at birth were randomly assigned to receive one of two preterm infant formulars: S26 Low Birthweight (S26-LBW, 25 infants) or Enfalac Premature (EPF, 24 infants). They were either exclusively formula-fed (13 infants) or the formula was used to supplement their own mother's fresh breast milk (36 infants). The mean age when milk feeds were commenced was 7 days and the mean age when birthweight was regained was 12 days. The mean age when 2000 g was reached was 45 days at which time 10 (20%) infants were below the tenth centile on the intrauterine growth chart. None of the above variables were significantly different between the S26-LBW and EPF groups. However, the S26-LBW group established full enteral feeding significantly earlier compared to the EPF group (42 versus 64 d) and the number with adverse gastrointestinal effects was lower (4 versus 10 infants). Both preterm infant formulas supported a growth rate in excess of that in utero without stressing the infants' metabolic system. The growth rate of infants fed preterm breast milk supplemented with preterm infant formula was quantitatively similar to those exclusively fed preterm infant formula.

Bottle Feeding↗

PubMed1989

Complementary DNA structure of the high molecular weight rat insulin-like growth factor binding protein (IGF-BP3) and tissue distribution of its mRNA.

Insulin-like growth factors (IGFs) found in extracellular fluids are bound to specific binding proteins. Recently a high molecular weight IGF-binding protein (IGF-BP3) has been isolated from porcine ovarian follicular fluid based on its inhibition of follicle stimulating hormone-stimulated estradiol production in rat granulosa cells. The complete primary structure of the porcine IGF-BP3 was deduced by molecular cloning. Using the porcine cDNA as a probe, we have now isolated and characterized cDNAs encoding rat IGF-BP3 from a pregnant mare serum gonadotropin-stimulated ovarian library. The predicted amino acid sequence revealed a mature polypeptide consisting of 265 amino acids with 18 cysteines and 4 potential Asn-linked glycosylation sites. Northern analysis of the IGF-BP3 mRNA in rat tissues showed a single 2.6 kb band in liver, kidney, stomach, heart, adrenal, ovary, testis, spleen, lung, small and large intestine in varying amounts, but the message is below the limit of detection in hypothalamus and brain cortex.

Amino Acid Sequence↗

PubMed1989

Prenatal ultrasonographic diagnosis of thoracopagus conjoined twins.

Conjoined twins are a rare obstetric event occurring 1/50,000 to 1/60,000 deliveries as a result of incomplete fission of the embryonic disc before the third week of pregnancy. They belong to the monochorionic-monoamniotic type of monozygotic twins and are classified according to the area of union, the most common site being the chest and upper abdomen (thoracopagus). Reported are two cases of thoracopagus twins in which the diagnosis was made prenatally by ultrasound in the second trimester of pregnancy. The most significant ultrasound findings included the demonstration of a single cardiac activity, the inability to separate the fetal bodies at their ventral portion, and a face-to-face fetal position. The pregnancies were allowed to continue until term with no significant prenatal complications, and an elective cesarean section was performed to avoid a traumatic delivery. In both cases the infants died during the first week of life because of cardiorespiratory insufficiency. The ultrasound criteria for the antenatal diagnosis of conjoined twins are reviewed, concluding that the careful ultrasound examination of all identified sets of twins, specially in those cases in which no separating membrane is demonstrated, is the cornerstone in making the prenatal diagnosis. In addition, ultrasound plays a crucial role not only in the diagnosis, but also in establishing the degree of conjoining, which is essential for planning an appropriate obstetrical and perinatal management.

Adult↗

PubMed1988

Complementary DNA cloning and sequencing of rat ovarian basic fibroblast growth factor and tissue distribution study of its mRNA.

Three cDNA clones encoding rat basic fibroblast growth factor (FGF) were isolated from 10(6) independent clones prepared from a pregnant mare serum gonadotropin (PMSG)-stimulated rat ovarian cDNA library. One of the cDNA clones contained the entire coding sequence for basic FGF. The other two possessed the sequence coding the carboxy terminal 61 amino acids of rat basic FGF, the putative upstream intron sequence, and a 3'-noncoding region. The cDNAs encoding rat basic FGF predict a molecule consisting of 154 amino acid residues, which is one amino acid shorter than the human and bovine basic FGF. Otherwise, there are only 5 conservative amino acid substitutions between the rat and the human/bovine sequences. Poly A+ RNA from brain cortex and hypothalamus show a single 6.0 kb band that hybridizes to the cloned cDNA probe by Northern analyses. The observation that basic FGF mRNA is below the limits of detection in adrenal, spleen, heart, lung, kidney, liver, stomach, small intestine, large intestine, testis, and ovary support the notion that the that the high levels of the protein found in these tissues is due to storage of the mitogen in the extracellular matrix and not continuous gene expression. The significance of the abundance of mRNA in tissues which are not undergoing either active angiogenesis or cell proliferation (hypothalamus and brain cortex) is unclear but emphasizes the potential neuronotrophic function of basic FGF.

Animals↗

PubMed1988

Porcine follistatin gene structure supports two forms of mature follistatin produced by alternative splicing.

Follistatin (FS), a novel gonadal protein which inhibits specifically the secretion of pituitary follicle stimulating hormone (FSH), has recently been isolated from porcine follicular fluid. cDNA cloning of the porcine ovarian FS precursor revealed two populations of cDNAs which differed at the 3'-region of the open reading frames; one population encodes a precursor of 317 amino acids while the other encodes another precursor having the same 317 amino acids, but with an additional 27 amino acids at the carboxy-terminal. Herein, we report the cloning of the porcine FS gene whose DNA structure reveals that the two populations of mRNA are generated by alternative splicing. In addition, restriction endonuclease mapping and DNA sequencing show that the FS gene is approximately 6 Kb long and consists of six exons separated by five introns. The first exon encodes the putative signal sequence, followed by four exons which encode the four domains of FS, three of which are highly homologous to each other. The last exon encodes the extra 27-amino acid carboxy-terminal domain of the 344-residued precursor.

Amino Acid Sequence↗

PubMed1988

Thyroid function in very preterm infants.

Indices of thyroid function were measured in 108 infants born at 23-31 weeks gestation, after birth, at 24 and 72 h, and at 1, 3, 4, 5 and 6 weeks of age. This group was characterised by low serum thyroxine (T4), normal thyroid stimulating hormone (TSH), low-normal thyroid binding globulin (TBG), low free thyroxine index (FTI) and low triiodothyronine (T3). The incidence of hypothyroxinaemia defined as a serum T4 value of less than 65 nmol/l was 58% after birth, increasing to 84% at 1 week, after which there was progressive reduction to 36% by 6 weeks of age. Mean T4 values were inversely proportional to gestational age during this study period. Infants of 23-28 weeks gestation had significantly lower T4, TBG, FTI and T3 values compared to those of 29-31 weeks gestation. Infants who had hyaline membrane disease (HMD) had significantly lower T4 and FTI values compared to those without HMD for up to 3 weeks of age. Similar differences were found between deaths and survivors in the first week after birth. This study suggests that there is increasing delay in maturation of the hypothalamic-pituitary-thyroid axis control with increasing prematurity. In addition, the data suggest that infants who were extremely preterm or those with HMD had worse and more persistent abnormalities of thyroid function secondary to their illness and metabolic stress. The significance of our findings, in particular that of prolonged hypothyroxinaemia, is uncertain. The role of thyroid replacement therapy in these very preterm infants therefore need to be assessed with a randomised clinical trial.

Age Factors↗

PubMed1988

Primary structure of the human follistatin precursor and its genomic organization.

Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. By use of the recently characterized porcine follistatin cDNA as a probe to screen a human testis cDNA library and a genomic library, the structure of the complete human follistatin precursor as well as its genomic organization have been determined. Three of eight cDNA clones that were sequenced predicted a precursor with 344 amino acids, whereas the remaining five cDNA clones encoded a 317 amino acid precursor, resulting from alternative splicing of the precursor mRNA. Mature follistatins contain four contiguous domains that are encoded by precisely separated exons; three of the domains are highly similar to each other, as well as to human epidermal growth factor and human pancreatic secretory trypsin inhibitor. The genomic organization of the human follistatin is similar to that of the human epidermal growth factor gene and thus supports the notion of exon shuffling during evolution.

Adult↗

PubMed1987

Symptomatic hypothyroxinemia with normal TSH levels in preterm infants.

The authors report eight preterm infants with hypothyroxinemia who developed clinical features similar to those described in congenital hypothyroidism: prolonged jaundice, hypoactivity, lethargy, constipation, edema, and hoarse cry. All had low serum thyroxine, normal thyroid stimulating hormone, and normal thyroid binding globulin levels. After exclusion of other causes for the symptoms, thyroid replacement therapy was started, resulting in rapid resolution of symptoms and return to euthyroid status. Follow-up of these infants after cessation of therapy revealed normal growth and development and normal thyroid function. The authors therefore recommend a prospective study to investigate the incidence of hypothyroxinemia, frequency of associated clinical features, and the benefits of thyroid replacement therapy based on a randomized controlled trial.

Humans↗

PubMed1987

Structural characterization of follistatin: a novel follicle-stimulating hormone release-inhibiting polypeptide from the gonad.

Follistatin, a novel, single chain, glycosylated polypeptide bearing no homology with previously characterized inhibins but exhibiting potent and specific pituitary FSH-release inhibition has been structurally characterized by protein microsequencing, cDNA cloning, and DNA sequencing. Two populations of clones differing in their 3'-untranslated sequences were found to encode a 344 amino acid precursor protein and an identical but carboxyl terminal truncated 317 amino acid precursor, respectively. Additionally, one clone, FS18, contained two introns and probably resulted from reverse transcription of heterogeneous nuclear RNA during cDNA library construction. Follistatin is unusually cysteine-rich, containing 36 cysteines in the mature coding sequence of 315 amino acids and an extremely acidic carboxyl terminal region, FS(292-304), comprised of Glu-Asp-Thr-Glu-Glu-Glu-Glu-Glu-Asp-Glu-Asp-Gln-Asp which probably resides outside a tightly cross-linked protein sphere. The heparin-binding ability of follistatin can probably be ascribed to the basic region specified by FS(75-86), Lys-Lys-Cys-Arg-Met-Asn-Lys-Lys-Asn-Lys. Overall, follistatin is organized into three homologous domains, FS(66-135), FS(139-210), and FS(216-287) containing 70, 72, and 72 amino acids, respectively, which show a 52% homology among themselves and a 57% homology with the 56 amino acid human pancreatic secretory trypsin inhibitor protein when aligned for maximum homology.

Amino Acid Sequence↗

PubMed1987

Complementary deoxyribonucleic acid (cDNA) cloning and DNA sequence analysis of rat ovarian inhibins.

Two forms of inhibin (A and B), gonadal polypeptide hormones that selectively suppress the secretion of FSH from the anterior pituitary, have been characterized from the porcine and human species, each being composed of a common alpha-chain and one of two distinct, but homologous beta-chains, i.e. alpha beta A and alpha beta B. Using cDNAs encoding the porcine inhibin subunits we have cloned and sequenced the cDNAs encoding the alpha, beta A, and beta B chains of rat ovarian inhibin. Northern analyses of rat testicular RNA with rat ovarian cDNA probes show the presence of mRNAs encoding alpha and beta B chains, but no detectable mRNA encoding the beta A chain under our experimental conditions. This suggests that there may be specific and distinct physiological roles for inhibins A and B. In addition, if there is no extratesticular source of beta A mRNA, then the male rat may be devoid of the stimulators of the secretion of FSH, i.e. activin (beta A beta B) and homoactivin A (beta A beta A), which are derived from the beta subunits of the two inhibins.

Amino Acid Sequence↗

PubMed1986

Cloning and DNA sequence analysis of the cDNA for the precursor of the beta chain of bovine follicle stimulating hormone.

Follicle stimulating hormone (FSH) plays essential roles in the maintenance and development of oocytes and spermatozoa in normal reproductive physiology. FSH possesses two subunits, alpha and beta, the latter being responsible for FSH biological specificity. We have cloned and sequenced the cDNA encoding the FSH beta chain from a bovine anterior pituitary cDNA library. The mature molecule is 109 amino acids long and is preceded by a 20-amino acid putative signal peptide. RNA gel blot analysis of bovine pituitary RNA shows that the mRNA encoding beta chain of FSH is approximately 1.7 kilobases in length.

Amino Acid Sequence↗