Renormalization-group equations in broken supersymmetric theories using superspace methods.
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Biomedical subjects
Publications and source records attributed to D Chang.
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An analog of human alpha-and beta-interferons (IFN-alpha and -beta) (generally consisting of the most frequently observed amino acid residue at each position in the molecule) has pronounced antiviral and antiproliferative activity in human and hamster cells. Intraperitoneal administration of this analog (designated IFN-alpha Con 1) to hamsters at 10(6) to 10(8) U/kg resulted in proportional increases in plasma concentrations through 6 h of monitoring. IFN-alpha Con 1 at these doses effectively limited encephalomyocarditis virus (EMCV) infections of hamsters. A natural human IFN-alpha preparation was also active against virus infections in hamsters. The antitumor activity of IFN-alpha Con 1 and natural human IFN-alpha was assessed in hamsters inoculated with lethal TBD932 lymphosarcoma. Various IFN treatment schedules resulted in prolonged survival following tumor challenge. IFN-alpha Con 1 administered at 10(5) to 10(6) U/hamster daily for 9-12 days following tumor challenge was effective in delaying tumor development, as was a natural human IFN-alpha preparation. The efficacies of combined IFN and cyclophosphamide therapies were determined. Unlike the natural human subtype IFN-alpha A, IFN-alpha Con 1 did not diminish the efficacy of cyclophosphamide (2.5 mg/hamster for 3 days) against the lymphosarcoma. However, an ineffective dose of cyclophosphamide (0.05 mg/hamster for 3 days) when combined with IFN-alpha Con 1 treatment showed enhanced antitumor activity. Combinations of cimetidine (16 mg/hamster for 4 days) and IFN-alpha Con 1 treatment did not prolong survival in this model system.
Structural properties and activity of recombinant human interferon-gamma (IFN-gamma) purified from Chinese hamster ovary (CHO) cells or a natural source were determined and compared with those of Escherichia coli-derived IFN-gamma. One preparation of CHO-derived IFN-gamma showed three bands, with the middle band being a doublet, in a SDS-polyacrylamide gel. The two higher-molecular-weight bands were shown to be glycosylated. Western blot analysis indicated that the three bands are IFN-gamma and lack an intact carboxyl terminus. The circular dichroic (CD) spectra showed that conformation of the CHO-derived IFN-gamma is similar in the native state, in acid, and after renaturation from acid to the E. coli-derived IFN-gamma. These results indicate that neither glycosylation nor carboxy-terminal processing affects conformational properties of the protein, as detected by CD spectroscopy. However, the antiviral activity was fourfold lower for the preparation of CHO-derived IFN-gamma than for the E. coli-derived IFN-gamma. A different preparation or a natural IFN-gamma preparation with less extensive carboxy-terminal processing showed similar conformational properties and antiviral activity to the E. coli-derived IFN-gamma. These results indicate that the carboxyl terminus, but not glycosylation, plays an important role in the antiviral activity of IFN-gamma.
Three series of experiments were performed in conscious dogs to test the possibility that the stimulation of adrenocorticotropin (ACTH) release by angiotensin II (ANG II) is mediated by arginine vasopressin (AVP). In the first protocol, the effect of ANG II on ACTH release was studied in dogs in which endogenous AVP levels had been increased by water deprivation. Water deprivation for 24 h increased plasma AVP concentration from 3.0 +/- 0.5 to 7.7 +/- 0.5 pg/ml (P less than 0.01) and increased the AVP response to the highest dose of ANG II (20 ng X kg-1 X min-1). Despite these changes, water deprivation failed to increase the ACTH response to ANG II. Next, the contribution of endogenous AVP to the stimulation of ACTH release by ANG II was examined using the V1-receptor antagonist, d(CH2)5Tyr[Met]-AVP (10 micrograms/kg iv). The ACTH response to ANG II in the presence of the AVP antagonist (66.4 +/- 3.1 to 100.1 +/- 15.9 pg/ml) was not significantly less than that in its absence (53.0 +/- 4.8 to 72.2 +/- 11.1 pg/ml). Finally, ANG II and AVP were infused in combination to determine whether there is a synergism between these two peptides in the release of ACTH. In one protocol, AVP and ANG II were infused separately and in combination. The ACTH response to ANG II and AVP in combination (48.7 +/- 6.5 to 61.5 +/- 8.5 pg/ml) was not enhanced compared with the responses to ANG II (59.8 +/- 7.3 to 71.0 +/- 10.1 pg/ml) or AVP (48.8 +/- 5.7 to 55.6 +/- 6.5 pg/ml) alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Elevation of brain catecholamine levels by systemic administration of L-dopa in dogs pretreated with the dopa decarboxylase inhibitor carbidopa inhibits the secretion of vasopressin and adrenocorticotropic hormone (ACTH) and decreases arterial blood pressure. The aim of the present study was to determine whether the inhibition of vasopressin secretion is mediated by dopamine or norepinephrine, both of which have been implicated in the control of vasopressin secretion, and whether the decrease in vasopressin secretion contributes to the suppression of ACTH secretion and fall in blood pressure produced by L-dopa. This was accomplished by comparing the effects of dopamine and alpha-adrenergic receptor antagonists on vasopressin, ACTH, and blood pressure responses to L-dopa. The effect of a specific antagonist of the vasoconstrictor action of vasopressin also was studied. Injection of L-dopa (20 mg/kg i.v.) in dogs pretreated with carbidopa (20 mg/kg i.v.) caused reductions in plasma vasopressin concentration (from 16.0 +/- 4.8 to 3.8 +/- 0.9 pg/ml; p less than 0.05), plasma ACTH concentration (from 96.0 +/- 20.4 to 49.2 +/- 10.0 pg/ml; p less than 0.05), and mean arterial pressure (from 121 +/- 6 to 78 +/- 5 mm Hg; p less than 0.05). Pretreatment with pimozide (1 mg/kg i.p.) completely blocked the inhibition of vasopressin secretion by L-dopa but failed to block the suppression of ACTH secretion (57.6 +/- 11.8 to 34.0 +/- 5.1 pg/ml; p less than 0.05) or the decrease in mean arterial pressure (126 +/- 5 to 93 +/- 7 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary basement membranes are believed to play important roles in lung morphogenesis, in maintenance of lung alveolar architecture, and in repair after pulmonary injury. However, very little is known about the synthesis and matrix deposition of lung basement membrane macromolecules. Accordingly, we have investigated the synthesis of type IV procollagen, the major collagenous component of basement membranes, in slices of adult rat lung. After a 4-h labeling with [3H]proline, type IV procollagen chains were extracted from lung homogenates with 2 M guanidine-HCl and purified by salt fractionation and ion exchange chromatography. The chains comigrated with authentic type IV chains by SDS-PAGE and were selectively coprecipitated with antibodies to type IV collagen. Peptide mapping confirmed their identity as pro alpha 1(IV) and pro alpha 2(IV), and suggested that the chains are predominantly assembled as heteropolymers. There was no evidence for proteolytic processing of the newly synthesized type IV procollagen even though type I and III procollagens were rapidly processed to lower molecular weight intermediates and collagen. Type IV procollagen accounted for approximately 40% of the extracted radiolabeled collagen, suggesting that there may be a relatively high turnover of lung basement membrane collagen in vivo.
We measured thyrotropin (TSH) with an enhanced luminometric assay ("Amerlite"; Amersham International). The detection limit of the assay is 0.02 milli-int. unit/L. Within-assay precision was 6.7 and 7.8% at 3.77 and 12.1 milli-int units/L, respectively, and between-assay precision was almost identical, whether singleton or duplicate samples were assayed. TSH measured in 132 euthyroid subjects ranged from 0.06 to 4.13 milli-int. units/L (mean 1.52, SD 0.86). Similar concentrations were found in 20 healthy pregnant women and 19 of 20 healthy post-menopausal women (one of whom had undetectable TSH). In 17 patients with primary hypothyroidism, TSH concentrations ranged from 9.34 to greater than 200 milli-int. units/L; and in 53 of 59 patients with hyperthyroidism, TSH concentrations were undetectable, ranging in the remaining six from 0.03 to 0.06 milli-int. unit/L. Results for TSH in 28 patients stimulated with thyroliberin were consonant with the results of the thyroliberin test in 25 cases. Thus, for most patients, measurement of a basal TSH concentration evidently will predict their thyroidal status and also the response to thyroliberin, but a few will require additional tests of thyroid function.
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His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH both in vivo and in vitro in pituitary incubates. In this study, for the first time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. In this assay system, the ED50 for GH-RP-6 was 9 nM, and the ED50 for hp-GRF-44 was 1.6 nM. Calcium-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 down regulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. These results suggest that GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.
A 47-year-old Cambodian refugee presented with an acute respiratory illness that featured consolidation of the lower lobe of the left lung and progressive involvement of the adjacent pleura caused by Pseudomonas pseudomallei. Initial difficulty in identifying the organism resulted in an inadequate duration of therapy. Chronic pleural disease followed, and the organism became resistant to many antibiotics during therapy. A diagnosis of pleuropulmonary melioidosis should be entertained and the microbiology laboratory alerted when patients with pneumonia who are from endemic areas are encountered, so that a diagnosis can be made early and the appropriate treatment begun.