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Biomedical subjects

J Y Chu

Publications and source records attributed to J Y Chu.

At least 37 records · Page 2Linked to original sources

Paroxysmal nocturnal hemoglobinuria associated with venous thrombosis and papillary endothelial hyperplasia presenting as ulcerated duodenal mass.

Paroxysmal nocturnal hemoglobinuria is an acquired clonal expansion of bone marrow stem cells that are deficient in the decay-accelerating factor, which is a complement regulatory glycoprotein (CD55), as well as in the membrane inhibitor of reactive lysis (CD59) and the C8-binding protein. These proteins are deficient on the membranes of red blood cells, granulocytes, monocytes, and platelets. The disorder is associated with intermittent hemolytic anemia, hemoglobinuria, infection, a tendency toward bone marrow aplasia, and venous thromboses. The thromboses, on resolution, may give rise to endothelial proliferation that may cause ischemia and ulceration, or, alternatively, the thromboses may cause ulceration leading to a granulation tissue response with exaggerated endothelial proliferation. We report a second case of paroxysmal nocturnal hemoglobinuria that presented roentgenographically as an ulcerated circumferential duodenal mass secondary to venous thrombosis accompanied by florid papillary endothelial hyperplasia. We also review the literature concerning this phenomenon.

Adolescent↗

Renal biopsy diagnosis of acute lymphocytic leukemia.

Hyperuricemia, due to inborn errors of metabolism, dehydration, or tumor lysis, may cause renal insufficiency. Hyperuricemia from tumor lysis syndrome in malignancy is usually associated with electrolyte disturbances such as hyperkalemia, hyperphosphatemia or hyper or hypocalcemia. Tumor infiltration into the kidneys can occur, yet this accounts for renal insufficiency in only 1% of patients. This infiltration of tumor cells into the kidneys is usually associated with evidence of malignancy elsewhere as identified by physical exam, radiographic studies, and examination of the peripheral smear or bone marrow. We report an unusual presentation of a child with acute lymphocytic leukemia presenting with acute renal failure, nephromegaly and hyperuricemia without electrolyte disturbances or systemic evidence of tumor elsewhere. We stress the importance of kidney biopsy in order to identify the etiology of the renal failure and hyperuricemia.

Acute Kidney Injury↗

Acetylation phenotype in hypertensive patients.

Individual differences in drug-metabolizing capacity may be due to the occurrence of genetic enzyme variants. This study of pharmacogenetics in this paper explores the polymorphic acetylation of hypertensive patients who had taken hydralazine as an antihypertensive drug in the cardiovascular clinic at Chinese Air Force General Hospital. An apparent bimodal distribution of acetylator phenotype was found in 96 subjects (26 slow and 70 fast acetylators) from measuring the percentage of acetylation of sulphamethazine (SMZ) in 6-hr blood, 3-to-6 hr urine samples; and the elimination half-life (t1/2) of SMZ; after administration of SMZ 10 mg/kg. The results might provide a therapeutic index of hydralazine and reduce the probability of drug-induced lupus erythematosus.

Acetylation↗

Monoclonal anti-human T cell antibody and PAP-s conjugate--preparation and selective cytotoxic properties on leukemic cell.

Pokeweed antiviral protein (PAP-s) was prepared from seeds of Phytolacca americana. Monoclonal antibody against human pan-T lymphocyte Wu71 was linked to PAP-s by a disulfide bond. The results of SDS-PAGE, double immunodiffusion of active monoclonal antibody and PAP-s showed that the conjugate was highly cytotoxic to the human T-leukemic cell line CEM, but not to antigen-negative cell line SP2/O. At a concentration of 10(-9) mol/L, 76.4% of the target cells were killed, as compared with 10.1% at 10(-9) mol/L of free PAP-s. Treatment of the CEM cells with conjugate at 10(-9) mol/L reduced their rate of protein synthesis by 72.4%, as determined with 14C-leucine incorporation. The immunotoxin may be useful for the in-vitro eradication of leukemic cells in autologous bone marrow transplantation to leukemia patients.

Antibodies, Monoclonal↗

A novel Fmoc-based anchorage for the synthesis of protected peptides on solid phase.

A novel bifunctional compound, 9-(hydroxymethyl)-2-fluoreneacetic acid, was synthesized, coupled to benzhydrylamine-resin, and evaluated for its application to the solid phase synthesis of protected peptide fragments. Anchor-bond cleavage was achieved with 15% piperidine/DMF. A protected heptapeptide, Boc-Val-Val-Ser(Bzl)-His(Tos)-Phe-Asn-Lys-(Z)-OH, corresponding to the sequence (1-7) of rat-transforming growth factor-alpha, was synthesized using this new support with an overall yield of 46%.

Amino Acids↗

Increased potency of antagonists of substance P having asparagine in position 6.

The general structure of antagonists of substance P (SP) which was found with the development of Spantide and analogs based on Spantide served for further refinement. The antagonistic potency was tested in vitro on guinea pig ileum and taenia coli. It was unexpectedly found that introduction of Asn6 gave rise to a considerable increase in potency. The exchange of Gln6 for Asn6 entails the shortening of the side chain by one CH2 unit and seems slight for steric advantages and potency increase. The analog [D-Arg1,D-Cl2Phe5,Asn6,D-Trp7,9,Nle11]SP had pA2 values of 7.4 (ileum) and 8.0 (taenia coli). We then used this sequence as a new lead to introduce new changes, which were made in positions 1, 3, 5, 7 and 9. It was found that Arg1 is important, but Lys3 can be exchanged. The Pal3 derivative had pA2 values of 8.1 and 8.0 and the Nle3 counterpart had 7.7 and 7.4 D-Cl2Phe is an effective substituent in position 5. D-Trp in positions 7 and 9 were superior to other alternatives.

Amino Acid Sequence↗

Temperature and adrenoceptors in the frog heart.

1. Cardiac adrenergic receptors in a frog, Rana tigrina, were examined in winter and summer months using isolated atria preparation maintained at 24 degrees, 14 degrees and 6 degrees C. Treatments included an examination of the atrial responses to selective alpha and beta adrenergic agonists (phenylephrine and isoproterenol respectively) and antagonists (phentolamine and propranolol). 2. Basal atrial beating rates differed between summer and winter months and increased with temperature. 3. Phenylephrine produced dose-dependent increases in the atrial beating rate and tension in the winter frogs only at 6 degrees C. These increases were blunted by phentolamine. 4. Isoproterenol produced positive chronotropic effects of 14 degrees and 24 degrees C but not at 6 degrees C in both summer and winter frogs; these effects were abolished by propranolol. Further, at 6 degrees C, the contractile response of the atrial tissue to isoproterenol was very sensitive. 5. Data suggests that the alpha adrenoceptor might be physiologically important to the frog in the low temperature environment of the cold season, during which period the cardiac beta adrenergic activity would be minimal or even absent.

Animals↗

[Design and synthesis of LHRH analogs].

In the hope to find new superagonists of LHRH, here we report the synthesis of six analogs by changing residue 5 of [D-Trp6 (or D-Arg6), des-Gly10]-LHRH-EA. For the convenience of comparison, the known compound [D-Trp6, desGly10]-LHRH-EA was also synthesized.

Animals↗

Blockade of sensory nerve mediated contraction of the rabbit iris sphincter by a series of novel tachykinin antagonists.

Electrical stimulation of the isolated rabbit iris sphincter muscle in the presence of atropine gives rise to a contraction that can be blocked by tachykinin antagonists. The ability of a series of novel tachykinin antagonists to inhibit the contractile effect of SP on the guinea-pig taenia coli and to suppress the electrically evoked contraction of the atropinized rabbit iris sphincter was tested. Several of the novel antagonists were found to be more potent in terms of pA2 and pIC50 values than the two previously described analogs, [D-Pro2, D-Trp7,9]SP9(1-11) and [D-Arg1, D-Trp7,9, Leu11]SP-(1-11) (Spantide). Apart from D-Trp in positions 7 and 9 the characteristic features of the potent novel antagonists were D-Cl2Phe (or D-Cys(Bzl] in position 5, Asn in position 6 and Nle in position 11. In addition Pal in position 3 seemed to offer an enhanced potency.

Animals↗

Effect of neonatal monosodium-L-glutamate treatment on the response of isolated uterine preparation to various uterine contraction stimulators.

1. The uterine activity of rats treated neonatally with MSG was examined in vitro by measuring the contractile response of the tissue to hormone/chemical stimulation. 2. The uterine responses to ACh and ANG II remained unchanged following neonatal MSG treatment while those to PGF2 alpha were sensitized. 3. The responses to OT and 5-HT were characterized by a reduction of the maximal contractile force and the rate of change in tension increased and decreased compared with the control with OT and 5-HT respectively. 4. Data suggested that these changes on uterine contractility could be ascribed to various possible mechanisms of action of MSG.

Acetylcholine↗

Successful chemotherapeutic decompression of epidural malignant germ cell tumor.

A patient with a sacrococcygeal malignant germ cell tumor developed epidural spinal cord compression syndrome 32 days after surgical resection of tumor. Rapid resolution of symptoms was observed after chemotherapy with vinblastine, bleomycin, and cisplatinum. There was no radiation therapy or laminectomy for spinal compression. The patient had an excellent neurological recovery without any sequelae from spinal compression. Chemotherapy alone is an excellent approach to the management of epidural compression by malignant germ tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Congenital acute nonlymphoblastic leukemia with translocation (9;18).

Chromosome analysis is becoming an increasingly important tool in the diagnosis and treatment of childhood malignancies. This report illustrates a new translocation t(9;18) in a neonate with congenital acute nonlymphocytic leukemia, which predicted a bone marrow relapse in a normal appearing bone marrow.

Acute Disease↗

Purification and characterization of minor brain proteolipids: use of fast atom bombardment-mass spectrometry for peptide sequencing.

A combination of lipophilic gel permeation chromatography and ion-exchange chromatography in organic solvents was used to purify low molecular weight proteolipids from bovine brain. Cleavage peptides were purified by HPLC and studied mainly by the fast atom bombardment--mass spectrometry technique. A proteolipid of Mr 14 000 contains several peptides from the first 113 amino acids of the major myelin proteolipid (MMPL) plus an extra unknown blocked N-terminal peptide. A proteolipid of Mr 16 000 contains smaller peptides belonging to a C-terminal fragment of MMPL of about 160 residues. These two proteolipids do not seem to be artifacts from MMPL.

Amino Acids↗

Design and synthesis of antagonists of substance P.

Synthesis and bioassay of about 65 analogs of substance P (SP) over five years yielded the antagonist [D-Arg1,D-Trp7,9,Leu11]-SP, which was named Spantide, and which was used by many investigators as a "tool". Spantide served as a reference antagonist for the design of 47 new peptides toward the goal of more potent inhibitors. Designs emphasized analogs with D-Trp7, D-Trp9, D-Trp10, D-pClPhe10, Nle11, Leu11, Ile11 and Met11, etc. Twenty-one/47 antagonists were superior in potency to that of Spantide, the best was [D-Arg1,D-Na1(5), D-Trp7,9,Nle11]-SP which required a 255-fold increase in SP concentration to give 50% of the maximum response at a concentration of 10(-5)M of the antagonist; this potency is ca. 5 times that of Spantide. For certain, but not all pairs of undecapeptides and truncated analogs, the undecapeptides may be significantly more potent than the truncated counterparts.

Amino Acid Sequence↗