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Biomedical subjects

D L Nguyen

Publications and source records attributed to D L Nguyen.

17 recordsLinked to original sources
PubMed1998

Purification from human plasma of a hexapeptide that potentiates the sulfation and mitogenic activities of insulin-like growth factors.

The human plasma contains small peptide molecules known as low molecular weight growth factors synergistically increasing certain biological actions of insulin-like growth factors. In the present work we isolated and characterized a hexapeptide with HWESAS as structure. This purified peptide was absolutely necessary for the sulfation activity of insulin-like growth factor-I on chick embryo pelvic cartilages and improved the mitogenic activity of both insulin-like growth factors. The effects of this hexapeptide were confirmed by using the homologous synthetic peptide, that exhibited similar biological effects. Other synthetic peptides with structure derived from hexapeptide were shown to be active: the pentapeptide HWESA appeared more potent than the tripeptide HWE, which is about 170 to 200 times less active than the hexapeptide. The sequence of hexapeptide HWESAS is identified in only one human protein that is C3f, a fragment of C3 complement.

Animals↗
PubMed1997

Effect of glicentin, oxyntomodulin and related peptides on isolated gastric smooth muscle cells.

Glicentin (proglucagon 1-69 GLIC) and oxyntomodulin (proglucagon 33-69 or OXM) are two peptide hormones that are co-released from ileum and large intestine during digestion. They modulate in vivo gastric acid secretion and the gastro-pyloro-duodenal activity. The specificity of their effects is linked to the presence of their C-terminal octapepide. As yet, no isolated target cell that responds specifically to this family of peptides has been described. The present report describes the in vitro effect of human synthetic GLIC, OXM and octapeptide-bearing fragments on smooth muscle cells isolated from the rabbit antrum. GLIC or OXM decreased the mean length of the cells by: 13.9 +/- 0.8% and 15.5 +/- 0.9%, respectively - GLIC being 16 times more potent than OXM (respective EC50 values: 5 and 83 pM). The C-terminal fragments OXM(19-37) and OXM(30-37) were as efficient as GLIC or OXM. Their potencies were OXM = OXM(19-37)>>OXM(30-37). Glucagon, which corresponds to OXM without the C-terminal octapeptide, or glucagon-like peptide-1 (7-36 amide) did not have any effect. The response to OXM was not influenced by antagonists to muscarinic, cholecystokinin or substance P receptors. In conclusion, our studies demonstrate for the first time an isolated target cell that responds specifically to GLIC, OXM and other octapeptide-bearing peptides.

Animals↗
PubMed1991

Functional endothelin-1 receptors in rat astrocytoma C6.

Rat astrocytoma C6 cells have been recently identified as target cells for ET-1, which stimulates inositol lipid turnover in these cells. It is shown here that binding of ET-1 to high-affinity receptors on C6 cells leads to 40-45% inhibition of isoproterenol-induced intracellular cyclic AMP accumulation, as well as to stimulation of inositol lipid turnover, both effects characterized by an absolute requirement of extracellular calcium. Moreover, ET-1, which has been generally reported to have a mitogenic effect on a variety of target cells including primary rat astrocytes, is shown here to stimulate or, alternatively, inhibit DNA synthesis in C6 cells, depending on the subclone considered.

Animals↗
PubMed1988

Sonography of brain abscesses complicating Citrobacter neonatal meningitis.

The incidence of cerebral complications from citrobacter meningitis is high, and these problems are often difficult to diagnose clinically. Cranial sonography provides the ideal imaging modality to detect the early complications of meningitis and the problems that may occur during or after treatment. Early and serial use of cranial sonography should help to preserve brain tissue and minimize the long-term neurologic deficits that arise from this disease.

Brain↗
PubMed1987

Production and characterization of human renin antibodies with region-oriented synthetic peptides.

Polyclonal and monoclonal antibodies were raised against pure human renin, but nothing was known about the regions against which they were directed. Using a three-dimensional model of mouse submandibular renin, we selected seven peptide sequences as belonging to potential epitopes. The main criteria for their choice were the location of the peptide sequences near the catalytic region and on the surface of the renin molecule and their hydrophilicity. After transposition of the regions to the 340-amino acid sequence of human renin, the seven peptides (corresponding to amino acids 50-60, 63-71, 81-90, 118-126, 162-169, 247-255, and 287-295) were synthesized, coupled to bovine serum albumin, and injected into rabbits. Five of these peptides elicited antibodies, and 50-68% binding of the corresponding iodinated peptide was obtained with a 1:25 dilution of antiserum. The antisera titers ranged from 1:5,000 to 1:100,000 when tested by enzyme-linked immunosorbent assay. The same antisera bound 15-65% of labeled pure human renin at a final dilution of 1:2.5, the highest percentage being obtained with peptide 81-90 antiserum. At a 1:5 dilution, the five antisera inhibited renin activity by 23-68% in human plasma with a high renin activity (40 ng of angiotensin I/h/ml). At a final dilution of 1:50, peptide 81-90 antiserum was still capable of producing 25% inhibition. Purified IgG (0.6 mg) from this antiserum inhibited pure human renin activity by up to about 40%, as measured by its reaction with pure synthetic human tetradecapeptide substrate. Antigenic peptides that mimic a part of the human renin sequence, especially peptide 81-90 representing the "flap" covering the cleft between the two renin lobes, constitute promising tools for the development of a synthetic antirenin vaccine.

Amino Acid Sequence↗
PubMed1987

Serial sonograms to detect pancreatitis in children receiving L-asparaginase.

The clinical, laboratory, and ultrasonographic findings in children receiving L-asparaginase therapy were retrospectively reviewed and correlated to determine the diagnostic reliability and clinical usefulness of serial pancreatic sonograms in detecting L-asparaginase-induced pancreatitis. A total of 217 sonograms were obtained in 92 patients. Six of the 92 (6.5%) had L-asparaginase-induced pancreatitis. The diagnosis of pancreatitis was based solely on clinical symptoms in three patients, on clinical and laboratory findings in two, and on sonographic and laboratory findings in one. No confirmed cases of pancreatitis were detected solely by ultrasonography before clinical or laboratory evidence was obtained. Sonograms were useful only in confirming clinical and/or laboratory evidence of pancreatitis, but were of no value in making the early or preclinical diagnosis of drug-induced pancreatitis. We have discontinued the practice of obtaining routine serial pancreatic sonograms in children receiving L-asparaginase at our institution.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Pharmacokinetic research on Pharmachem's lincomycin hydrochloride in pigs].

In the experiments lincomycin hydrochloride LMC "F" with activity 820 UI/mg was used. It was established that in pigs, 5% water solution of LMC "F", applied intramuscularly in doses of 5 and 10 mg/kg m. and internally in doses 50 and 100 mg/kg m., penetrates comparatively quickly in the blood serum, and yet in the first hour established maximal concentrations. Intramuscular injection of LMC "F" of pigs, in doses of 5 and 10 mg/kg m., creates bacteriostatic concentrations in the blood serum for 12 hours, regardless of the quantity of the dose, and applied internally has a longer duration of the retention. The biological half-life of LMC "F" after muscular application in pigs is accordingly 1.7 and 3.5 hours, and after internal application 2.3 and 2.8 hours. Applied a single time intramuscularly in pigs in doses of 5 and 10 mg/kg m., LMC "F" is resorbed from the place of application and after 3 hours is established in most high quantities in the kidney in the lungs, the liver, the bile and in the urine. Mainly it is extracted with the urine in high concentrations--about 190 mg/cm3 (on the 3-rd hour), after intramuscular injection in dose of 10 mg/kg m. The longest time the antibiotic remains in the lungs, the urine and in the bile (up to 96 hours).

Administration, Oral↗
PubMed1986

Location of antigenic determinants on primary sequences of subunits of nicotinic acetylcholine receptor by peptide mapping.

The binding domains of 28 monoclonal antibodies (mAbs) against the alpha, beta, and delta subunits of the Torpedo acetylcholine receptor were mapped on the primary sequences of these subunits. Small peptide fragments (2000-20,000 daltons) of the purified subunits were obtained by digestion with staphylococcal V8 protease and papain, separated on a discontinuous polyacrylamide gel electrophoretic system, and electroblotted onto diaminophenyl thioether paper. The blots were probed with the various monoclonal antibodies and also with antibodies against carboxy-terminal decapeptides of the alpha, beta, and delta subunits to identify the carboxy-terminal fragments. From inspection of the binding patterns of the various antibodies to the subunits fragments and the molecular weights of these fragments, and by using the carboxy termini of the subunits as reference points, it was possible to deduce the regions on the primary sequence of each subunit in which the antibodies bound and in some cases to order the binding sites within these sequences. mAb 148, which inhibits receptor function by cross-linking receptor molecules on the cytoplasmic side, was mapped to the sequence beta 368-406. The main immunogenic region of the native receptor, which is of pathological importance in the autoimmune disease myasthenia gravis, was mapped by using mAb 210 to within 80 amino acid residues (alpha 46-127). The overall antigenic structure of alpha subunits was examined. Synthetic peptides have been used to locate determinants responsible for 83% of the antibodies in antisera to denatured alpha subunits and 46% of the antibodies to denatured alpha subunits in antisera to intact receptor. Theoretical models of the transmembrane orientation of the subunit polypeptide chains were tested by determining whether mapped monoclonal antibodies bound to the extracellular or intracellular surface of receptor-rich membranes. Our results confirm previous reports that the carboxy termini of the subunits are exposed on the intracellular surface, as is part of the region between a putative channel-forming domain (M5) and a putative membrane-spanning region (M3). However, contrary to current theoretical models, the region between M5 and the putative membrane-spanning sequence M4 also appears to be on the intracellular surface, implying that M4 and M5 are not membrane-spanning domains.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1986

Transmembrane topography of nicotinic acetylcholine receptor: immunochemical tests contradict theoretical predictions based on hydrophobicity profiles.

In our preceding paper [Ratnam, M., Sargent, P. B., Sarin, V., Fox, J. L., Le Nguyen, D., Rivier, J., Criado, M., & Lindstrom, J. (1986) Biochemistry (preceding paper in this issue)], we presented results from peptide mapping studies of purified subunits of the Torpedo acetylcholine receptor which suggested that the sequence beta 429-441 is on the cytoplasmic surface of the receptor. Since this finding contradicts earlier theoretical models of the transmembrane structure of the receptor, which placed this sequence of the beta subunit on the extracellular surface, we investigated the location of the corresponding sequence (389-408) and adjacent sequences of the alpha subunit by a more direct approach. We synthesized peptides including the sequences alpha 330-346, alpha 349-364, alpha 360-378, alpha 379-385, and alpha 389-408 and shorter parts of these peptides. These peptides corresponded to a highly immunogenic region, and by using 125I-labeled peptides as antigens, we were able to detect in our library of monoclonal antibodies to alpha subunits between two and six which bound specifically to each of these peptides, except alpha 389-408. We obtained antibodies specific for alpha 389-408 both from antisera against the denatured alpha subunit and from antisera made against the peptide. These antibodies were specific to alpha 389-396. In binding assays, antibodies specific for all of these five peptides bound to receptor-rich membrane vesicles only after permeabilization of the vesicles to permit access of the antibodies to the cytoplasmic surface of the receptors, suggesting that the receptor sequences which bound these antibodies were located on the intracellular side of the membrane. Electron microscopy using colloidal gold to visualize the bound antibodies was used to conclusively demonstrate that all of these sequences are exposed on the cytoplasmic surface of the receptor. These results, along with our previous demonstration that the C-terminal 10 amino acids of each subunit are exposed on the cytoplasmic surface, show that the hydrophobic domain M4 (alpha 409-426), previously predicted from hydropathy profiles to be transmembranous, does not, in fact, cross the membrane. Further, these results show that the putative amphipathic transmembrane domain M5 (alpha 364-399) also does not cross the membrane. Our results thus indicate that the transmembrane topology of a membrane protein cannot be deduced strictly from the hydropathy profile of its primary amino acid sequence. We present a model for the transmembrane orientation of receptor subunit polypeptide chains which is consistent with current data.

Animals↗
PubMed1986

Hepatic hemangioma. Diagnosis by emission computed tomography.

Hepatic hemangiomas in an asymptomatic patient usually require no treatment. Therefore, noninvasive diagnosis of this entity is critical to avoid an unnecessary diagnostic laparotomy and/or closed biopsy, the latter potentially leading to massive or fatal hemorrhage. Numerous authors have reported on the use of computed tomography, ultrasound, and planar nuclear imaging to establish this diagnosis (1,2,3). The findings in a case studied by all modalities, including SPECT imaging, are reported.

Adult↗
PubMed1986

Hepatoblastoma.

Hepatoblastoma is a rare hepatic tumor generally presenting during the first three years of life as an enlarging abdominal mass. Other symptoms are nonspecific; however, it may be associated with hemihypertrophy, virilization, and osteoporosis. The serum bilirubin infrequently is elevated, but up to 2/3's will have elevated serum alpha fetoprotein as a tumor marker. The overall survival rate is 35% in survivors who underwent a complete resection.

Carcinoma, Hepatocellular↗
PubMed1986

Sonography of the adrenal glands in chronic disseminated histoplasmosis.

In this retrospective study, the findings on abdominal sonograms in six patients newly diagnosed as having chronic disseminated histoplasmosis are reported. Five of six patients showed bilateral adrenal gland enlargement that was similar in degree from side to side. The most characteristic feature was the maintenance of a triangular shape in five glands and a cylindrical shape in two glands. Four glands had a nonspecific round or oval shape. All sonographic findings correlated well with the computed tomographic (CT) findings on each patient except that CT detected the one enlarged right adrenal gland not demonstrated sonographically. Abdominal sonography may provide the initial important clue to the diagnosis of chronic disseminated histoplasmosis.

Adrenal Gland Diseases↗
PubMedDate not supplied

Ultrasound diagnosis of immature cervical teratoma: a case report.

We report a case of cervical teratoma in a term female infant born to a 20-year-old white woman. There are rare tumors in neonates, occurring in approximately 1 in 20,000 to 1 in 40,000 live births. These tumors are accurately defined by ultrasound. Although benign, cervical teratomas cause respiratory compromise. In this case the tumor was removed surgically with no recurrence at the 10-month follow-up.

Adult↗