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Biomedical subjects

A Tseng

Publications and source records attributed to A Tseng.

At least 55 records · Page 3Linked to original sources

Pre- and postjunctional actions of neuropeptide Y and related peptides.

The effects of neuropeptide Y (NPY) and related peptide fragments on blood pressure and vagal action at the heart were compared in the anaesthetized rat. A change in vagal action was taken as a measure of presynaptic activity and a change in blood pressure was taken as a measure of postsynaptic activity. NPY, NPY-(13-36), PYY-(13-36), des-Ser22-NPY-(13-36) and a stabilized 13-36 analogue of NPY (ANA NPY) all exerted pressor actions and attenuated vagal action at the heart. The maximum vagal inhibitory or presynaptic action in order of potency was NPY, ANA-NPY, PYY-(13-36) significantly greater than NPY-(13-36), des-Ser22-NPY-(13-36). The order of potency for the half time of this effect was NPY, ANA-NPY significantly longer than PYY-(13-36) and NPY-(13-36), which were significantly longer than des Ser22-NPY-(13-36). For the pressor or postsynaptic effects, NPY increased blood pressure significantly more and for a longer duration than all the 13-36 fragments, which were not demonstrably different in this respect. These results are consistent with the proposal that there are two populations of NPY receptors. The C-terminal flanking peptide of NPY (CPON) and desamido-NPY had no effect on either vagal action at the heart or on blood pressure.

Animals↗

Recombinant interferon-gamma in the treatment of recurrent nasopharyngeal carcinoma.

The etiologic relationship of the Epstein-Barr virus (EBV) to nasopharyngeal carcinoma prompted this study of the efficacy of interferon-gamma (IFN-gamma), which possesses antiviral and antitumor activity, in the treatment of recurrent carcinoma. Fourteen patients received recombinant IFN-gamma in daily intramuscular doses of 5-10 X 10(6) U/m2. Of 13 patients evaluable for response, five had a minor response; disease was stable in two and had progressed in six. EBV serology for immunoglobin (Ig) G, IgA-VCA, and early antigen was measured in six patients. In four of these, titers rose consistently with disease progression and in one patient, titers decreased with minor response.

Adult↗

Intramedullary spinal cord metastasis in Hodgkin's disease. Rapid diagnosis and treatment resulting in neurologic recovery.

Intramedullary spinal cord metastases are uncommon in Hodgkin's disease and have a poor prognosis. This prognosis reflects the refractory or widely disseminated status of the disease at the time of development of neurological symptoms and difficulties in diagnosis. Computerized tomography and magnetic resonance imaging have enabled more rapid and specific diagnosis of spinal cord diseases. The authors report a patient who presented with Brown-Sequard syndrome due to intramedullary spinal cord infiltration from Hodgkin's disease. This patient was diagnosed promptly and with rapid initiation of radiation and chemotherapy, she has had neurologic recovery.

Adult↗

Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase.

The EJ-ras gene was placed under the transcriptional control of the steroid-inducible mouse mammary tumor virus promoter/enhancer and introduced into Rat-1 fibroblasts, yielding the 14C cell line. When these cells were exposed to dexamethasone in vitro, EJ-ras mRNA was induced 15- to 20-fold, the cells grew in agar, and, after injection of cells into syngenic Fischer 344 rats, they produced lethal fibrosarcomas. Inhibitors of poly(ADP ribose) polymerase, which prevent the activation of the purified enzyme by a synthetic octadeoxyribonucleotide duplex, inhibited both in vivo tumorigenicity and in vitro growth in soft agar. The enzyme inhibitor 1,2-benzopyrone, which was studied in detail, and other polymerase inhibitors had no effect on EJ-ras mRNA or p21 protein expression. Poly(ADP ribose) polymerase [NAD+:poly(adenosine diphosphate D-ribose) ADP-D-ribosyltransferase, EC 2.4.2.30] was inhibited by the drug in both untreated and dexamethasone-treated cells both in vitro and in vivo to the same extent, but biological consequences of enzyme inhibition were manifest only when the cells were in the transformed tumorigenic state.

Animals↗

Progestin-dependent effect of forskolin on human endometrial aromatase activity.

We have previously demonstrated that the aromatase activity in human endometrial stromal cells is stimulated by progestin and enhanced by oestrogen. In this study, we have investigated the effect of forskolin (Fk), an agent that stimulates the hormone-sensitive adenylate cyclase in mammalian cells, on the intracellular cAMP content and aromatase activity in endometrial stromal cells in primary culture. Stromal cells were isolated from proliferative and secretory endometria and were individually cultured in nutrient medium or medium supplemented with medroxyprogesterone acetate (MPA), oestradiol (E2) and Fk, separately or in combination. The intracellular cAMP content of stromal cells was increased after incubation with Fk. Stromal cells treated with Fk alone or FK and MPA for 1-3 days sustained the elevated intracellular cAMP content but 90% of this nucleotide was released to the medium. Aromatase activity was either not affected or was increased up to 5-fold over the control by Fk alone. Forskolin exerted a synergistic effect upon aromatase activity in the presence of progestin or progestin and oestradiol. Sequential incubation of the stromal cells with MPA and then Fk indicated that the additional increase in aromatase activity caused by Fk occurred after 24 h of incubation. These results demonstrate that intracellular cAMP exerts a stimulatory effect on aromatase activity in progestin-conditioned stromal cells. We also investigated whether the endometrial aromatase activity changes in vivo during the reproductive cycle by measuring the activities in endometrial specimens obtained from women during their reproductive age.(ABSTRACT TRUNCATED AT 250 WORDS)

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group.

Seventeen patients with advanced or recurrent salivary gland cancer were treated with cisplatin, doxorubicin, and 5-fluorouracil combination chemotherapy (PAF). Two patients achieved a complete response and four patients achieved a partial response, for an overall response rate of 35%. Six of the nine patients who received PAF in the neoadjuvant setting did not respond and proceeded to surgery and/or radiation therapy. No difference in response rate was found between those patients treated for recurrent disease v those treated with neoadjuvant chemotherapy. All three patients with adenocarcinoma responded. The response duration in patients with metastatic or recurrent disease ranged from 6 to 15 months. The PAF regimen was delivered primarily in the outpatient setting and was associated with acceptable toxicity. PAF demonstrates activity in salivary gland malignancies, and further evaluation of this combination seems warranted.

Adult↗

The amino acid sequence of Emu osteocalcin: gas phase sequencing of Gla-containing proteins.

Osteocalcin (OC), the major gamma carboxyglutamic acid (Gla)-containing protein of vertebrate bone, has been isolated from bones of the emu (Dromaius novaehollandae) and the primary structure determined by a combination of gas phase N-terminal sequencing of the intact molecule and a proteolytic fragment, and carboxypeptidase Y C-terminal sequencing. Gla residues were located by counting tritium radioactivity in fractions from the N-terminal sequencing of the tritiated/thermally decarboxylated molecule. Emu OC consists of 48 amino acid residues containing 3 Gla residues, and a single disulphide bond. The C-terminal 29 residues are identical to those of the human and sheep OC sequences. Alignment of the N-terminal sequence against those of other OCs reveals greater sequence homology with chicken OC than with mammalian OCs.

1-Carboxyglutamic Acid↗

Third-line chemotherapy for resistant Hodgkin's disease with lomustine, etoposide, and methotrexate.

Thirty-two patients with recurrent Hodgkin's disease have been treated with an oral regimen employing lomustine (CCNU, 100 mg/m2 orally on Day 1); etoposide (VP-16, 100 mg/m2 orally on Days 1-3 and 21-23); and methotrexate (30 mg/m2 orally on Days 1, 8, 21, and 28). The regimen was repeated every 6 weeks. Most patients had been treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); 20 had had prior irradiation. Lymph node was the predominant site of disease and the majority of patients had B symptoms. Four patients achieved complete response (13%), with a median duration of 33+ months, and 11 achieved partial response (34%), with a median duration of 5 months, for an overall response rate of 47%. The major toxic effect was severe myelosuppression, which occurred in six patients; there were no treatment-related deaths. This oral regimen was easy to administer in heavily pretreated patients with poor venous access and had minimal toxicity.

Administration, Oral↗

Modulation of fluoropyrimidine metabolism by chlorpromazine.

Chlorpromazine is a potent inhibitor of calmodulin and can alter the accumulation, metabolism, and incorporation into RNA of several fluoropyrimidine drugs. Using S-180 murine sarcoma cells, the accumulation of the base Fluorouracil and its metabolism to ribonucleotides is enhanced by chlorpromazine treatment, as measured by HPLC. In contrast, the accumulation and metabolism of the nucleoside Fluorouridine was suppressed by chlorpromazine. Cytotoxicity studies revealed that non-toxic concentrations of chlorpromazine were synergistic with Fluorouracil, but were antagonistic with Fluorouridine. These findings suggest that modulation by chlorpromazine of specific nucleoside kinase involved in Fluorouracil metabolism can result in increased therapeutic utility.

Animals↗

Vancomycin-induced neutropenia complicating bone marrow recovery in a patient with leukemia. Case report and review of the literature.

Neutropenia associated with intravenous vancomycin therapy is reported in a patient with chronic myelogenous leukemia. The patient received 12 days of vancomycin therapy without incidence; however, a second course of vancomycin initiated on hospital day 14 produced severe neutropenia. This delayed onset is typical of vancomycin-induced neutropenia. The neutropenia reversed, without complications, as soon as the vancomycin was discontinued.

Adult↗

Gynecomastia in testicular cancer patients. Prognostic and therapeutic implications.

Eighty-one patients with advanced testicular cancer were evaluated for gynecomastia or severe breast tenderness at diagnosis and after platinum-based chemotherapy. The prognostic significance of gynecomastia in these two settings was explored. At presentation, 10% (8 patients) had gynecomastia or breast tenderness and elevated HCG levels. The likelihood of gynecomastia was greater with increasing HCG level (P = 0.002). However, gynecomastia at presentation was a more powerful independent discriminant of poor survival than the initial HCG level by multivariate analysis (P = 0.004). Fifteen percent (12 patients) developed transient gynecomastia after chemotherapy not attributable to other known causes. HCG levels were normal. Endocrine evaluation typically revealed elevated FSH, LH, and estradiol/testosterone ratios. This may have reflected damage to testicular germinal epithelium. All 12 patients are alive without disease in contrast to the 8 patients who had gynecomastia at diagnosis. Therapy decisions should therefore be based on the time of onset of gynecomastia and in the context of appropriate clinical markers and evaluation.

Adolescent↗

The treatment of malignant histiocytosis.

Twenty-four consecutive cases of malignant histiocytosis (MH) treated at Stanford Medical Center between 1973 and 1983 have been reviewed. Most patients presented with systemic symptoms (91%) and advanced disease (stage IV, 80%). Multiple organ involvement was common. In six cases, pathologic tissue was further characterized by frozen section immune histochemistry, using a panel of monoclonal antibodies known to react with monocytes and macrophages, as well as a variety of hematopoietic cells. One case expressed a mature monocyte/macrophage phenotype; three cases were considered null cell or primitive lesions; and two cases were identified as probable T cell lymphomas. Seven patients underwent splenectomy. Two patients died prior to any treatment. Twenty-two patients were treated with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) +/- bleomycin (B), +/- midcycle high-dose methotrexate (HD-MTX) with leucovorin rescue. Seven patients received prophylactic intrathecal MTX. Of 22 evaluable patients, there was a 68% complete response rate (CR), a 23% partial response rate (PR), and a 9% no response rate (NR). Median duration of CR was 30+ months; median duration of PR was 2.4 months. Median survival for patients attaining a CR has not been reached v 3 months for the PR and NR groups. For all 24 patients, median survival was 2 years, with a 5-year actuarial survival of 40%. Multivariate analysis revealed that a platelet count less than 150,000 (P Cox = .005) and the dose of drug delivered (P Cox = .057) were the most important prognostic factors. Prophylactic intrathecal MTX therapy and splenectomy did not influence survival. Although MH is an aggressive disease with a poor prognosis, it is potentially curable. Systematic and aggressive treatment should further improve the outcome.

Adolescent↗

Extended cholecystectomy for carcinoma of the gallbladder.

We evaluated extended cholecystectomy, wedge resection of the gallbladder bed, and regional lymphadenectomy for carcinoma of the gallbladder. Between 1971 and 1993 we treated 227 patients, 59 of whom were treated with simple cholecystectomy and 66 with extended cholecystectomy. The tumors were classified according to the stages proposed by the Japanese Society of Biliary Surgery. For Stage I and II disease extended cholecystectomy had a better result than simple cholecystectomy. For the extended cholecystectomy cases the cumulative 5-year survival rate was 78.9% for Stage I, 63.6% for Stage II, 44.4% for Stage III, and 8.3% for Stage IV. The survival of Stage I patients was excellent. For cases more advanced than Stage II (S3, N2, Hinf1, and Binf1), the prognosis was significantly worse. In these cases more aggressive surgery may be needed.

Adult↗

A strategy for obtaining active mammalian enzyme from a fusion protein expressed in bacteria using phospholipase A2 as a model.

An active preparation of human phospholipase A2 (PLA2) was made after expression as an insoluble fusion protein in Escherichia coli. The new key elements required for PLA2 isolation were the maintenance of the fusion protein in solution after the initial solubilization and the use of a tryptophan cleavage procedure for regeneration of native PLA2 from the fusion protein. The fusion protein was composed of a beta-galactosidase leader peptide incorporating six consecutive threonine residues to aid in insoluble inclusion body formation, followed by a tryptophan adjacent to the N-terminus of PLA2. The fusion protein was purified from cell lysates, and the leader peptide was cleaved on the C-terminal side of the tryptophan residue with N-chlorosuccinimide. The released PLA2 was refolded and renatured to produce an enzyme with activity comparable to that of other phospholipases A2.

Amino Acid Sequence↗