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Biomedical subjects

H M Yang

Publications and source records attributed to H M Yang.

At least 73 records · Page 4Linked to original sources

Influence of endogenous angiotensin on the renovascular response to norepinephrine.

The purpose of this study was to elucidate the role of endogenous angiotensin II in mediating the renovascular effects of renal adrenergic stimulation. Six conscious dogs instrumented for monitoring of renal blood flow were subjected to step increases every 10 minutes in the rate of norepinephrine infusion into the renal artery. Under control conditions, infusion of norepinephrine (10-40 ng/min per milliliter per minute of control renal blood flow) increased plasma renin activity and decreased renal blood flow progressively by approximately 10-75%. When increments in angiotensin II during norepinephrine infusion were abolished by fixing plasma levels of angiotensin II at either normal or high concentrations by chronic infusion of captopril plus angiotensin II, renal blood flow responses to adrenergic stimulation were greatly attenuated at rates of norepinephrine infusion that decreased renal blood flow up to approximately 40% under control conditions. Thus, acutely generated angiotensin II appeared to contribute to the renovascular effects of norepinephrine. However, when endogenous levels of angiotensin II were suppressed to low levels by chronic infusion of captopril alone, norepinephrine induced severe renal ischemia at much lower rates of infusion than occurred when the renin-angiotensin system was intact. Since this enhanced sensitivity to norepinephrine did not occur during chronic captopril infusion when angiotensin II was given simultaneously at rates that restored mean arterial pressure to normotensive levels or higher, low arterial pressure during chronic captopril administration may predispose the kidneys to excessive renal vasoconstriction during renal adrenergic stimulation.

Angiotensin II↗

[Oxygen free radical injury after delayed fluid resuscitation in burn patients].

Sixty seven burn patients (TBSA > 30%) were entered in a prospective study. Among them, twenty seven experienced delayed fluid resuscitation (DFR group) and the rest had early resuscitation (non-DFR group). Oxygen free radical (OFR) content in the blood was measured with ESR technic, and levels of blood SOD, blood GSHpx, serum MDA were also determined. The results showed: 1 The morbidity and mortality of burn shock and MSOF were higher in DFR group as compared with non-DFR group. 2 There was a significant increase of blood OFR content subsequent to resuscitation in DFR group as compared with that in non-DFR group. 3 The level of MDA in the serum of patients with burn shock was higher in DFR group than that in non-DFR group. 4 In DFR group, the level of serum MDA is higher in patients who developed MSOF as compared with that in patients who did not develop MSOF. The data indicated that DFR augmented the morbidity and mortality of burn shock and MSOF, in which OFR might play a role.

Adolescent↗

Siderophore production by Pseudomonas pseudomallei.

Eighty-four strains of Pseudomonas pseudomallei isolated from patients with melioidosis were examined for siderophore production. All the strains were shown to produce siderophore both on chrome azurol S agar plates and in liquid medium under iron-deficient conditions. Chemical assays indicated that the siderophore belongs to the hydroxamate class. Addition of iron to the culture medium resulted in increased culture growth with markedly decreased yield of siderophore. Siderophore produced by strain U7 was purified by gel filtration chromatography, and the molecular weight was estimated to be 1,000. When this partially purified siderophore was added to culture medium, it promoted iron uptake by P. pseudomallei in the presence of EDTA and enhanced growth of the organism in the presence of transferrin. We have given this siderophore the trivial name malleobactin.

Catechols↗

Role of angiotensin in ameliorating the renal actions of norepinephrine.

To determine the importance of the arterial pressure effects of angiotensin II (ANG II) on renal function during acute renal adrenergic stimulation, we examined the effects of a 2-h intrarenal arterial infusion of norepinephrine (NE) at 0.1 and 0.25 micrograms.kg-1.min-1 on renal function in five conscious dogs during 1) control conditions, 2) servo-control of renal arterial pressure (RAP) at control levels, and 3) chronic captopril administration. The low rate of NE infusion produced an approximately 20% decrease in glomerular filtration rate (GFR) and renal plasma flow (RPF) and an approximately 8-mmHg increase in RAP in association with an approximately 2.5-fold rise in plasma renin activity (PRA). The high rate of NE infusion produced greater increments in both PRA and RAP and an approximately 50% reduction in GFR and RPF. Neither servo-control of RAP nor captopril administration significantly affected the above renal responses to the low rate of NE infusion. In marked contrast, when increases in RAP (approximately 20 mmHg) were prevented at the high rate of NE infusion by servo-control of RAP, both the PRA and renal responses were enhanced. Furthermore, when RAP was reduced (approximately 25 mmHg) as a result of chronically blocking the renin-angiotensin system with captopril, the renal responses to the high rate of NE infusion were exaggerated even further; in four of five dogs, total renal ischemia occurred in response to NE. These results indicate that ANG II indirectly ameliorates the renal actions of renal adrenergic stimulation by increasing RAP.

Angiotensin II↗

Preservation of renal function by angiotensin during chronic adrenergic stimulation.

The purpose of the present study was to determine the role of angiotensin II (Ang II) in mediating renal responses to chronic intrarenal norepinephrine infusion. Norepinephrine was continuously infused for 5 days into the renal artery of unilaterally nephrectomized dogs at progressively higher daily infusion rates: 0.05, 0.10, 0.20, 0.30, and 0.40 micrograms/kg/min. In three additional groups of dogs, norepinephrine infusion was repeated during chronic intravenous captopril administration to fix plasma Ang II concentration at 1) low levels (no Ang II infused), 2) high levels in the renal circulation (Ang II infused intrarenally at a rate of 1 ng/kg/min), and 3) high levels in the systemic circulation (Ang II infused intravenously at a rate of 5 ng/kg/min). In the control group of animals with intact renin-angiotensin systems, there were progressive increments in mean arterial pressure (from 96 +/- 4 to 141 +/- 6 mm Hg) and plasma renin activity (from 0.4 +/- 0.1 to 10.9 +/- 4.5 ng angiotensin I/ml/hr) and concomitant reductions in glomerular filtration rate and renal plasma flow to approximately 40% of control during the 5-day norepinephrine infusion period. In marked contrast, when captopril was infused chronically without Ang II, mean arterial pressure was 20-25 mm Hg less than that under control conditions, and the renal hemodynamic effects of norepinephrine were greatly exaggerated; by day 3 of norepinephrine infusion, both glomerular filtration rate (16 +/- 2% of control) and renal plasma flow (12 +/- 4% of control) were considerably lower than values in control animals (86 +/- 4% and 80 +/- 8% of control, respectively). Similarly, when a high level of Ang II was localized in the renal circulation during captopril administration, mean arterial pressure was depressed, and again there were pronounced renal responses to norepinephrine. Conversely, when Ang II was infused intravenously during captopril administration, mean arterial pressure was not reduced, and the glomerular filtration rate and renal plasma flow responses to norepinephrine were similar to those that occurred under control conditions. These findings indicate that the renin-angiotensin system prevents exaggerated renal vascular responses to chronic norepinephrine stimulation by preserving renal perfusion pressure.

Angiotensin II↗

A deletion panel of the long arm of the X chromosome: subregional localization of 22 DNA probes.

Two males and two females with different but overlapping deletions on the proximal long arm of the X chromosomes have been investigated. Their karyotypes, which have been well characterized by high resolution banding techniques, are 46,Y,del(X)(pter----q21.1::q21.33----qter); 46,Y,del(X)(pter----q21.2::q21.31----qter); 46,X,del(X)(pter----q21.31::q24.3----qter) and 46,X,del(X)(pter----q21.1:). A deletion panel, which makes it possible to subdivide the long arm of the X chromosome into seven subregions, has been established using the genomic DNA from the four families, and applied to the fine subregional localization of the loci for 22 DNA probes. Based on the results obtained, the possible location of the loci in question has been narrowed down considerably, in some cases to an area of only 5% of the previously assigned region; hybridization to Southern blots of a panel with well-characterized chromosome deletions is thus a powerful means of localizing DNA probes, especially with respect to the X probes.

Blotting, Southern↗

Exclusion mapping of 12 X-linked disease loci and 10 DNA probes from the long arm of the X-chromosome.

Specific chromosome rearrangements associated with disease entities are invaluable resources for physical mapping. A deletion on the X chromosome of a male leads to the nullisomy for X-linked genes, resulting in the onset of genetic diseases and/or the absence of the DNA probe detectable sequences. This permits the localization of these loci within the deleted area. On the other hand, the region for some other X-linked loci can be excluded from the deleted area according to the absence of the characteristic symptoms of the disease and/or the presence of the hybridization signals. An interstitial deletion on the long arm of the X chromosome of a male has been characterized by high resolution banding. The karyotype of the proband is 46,Y,del(X)(pter----q21.1::q21.33----qter). The regions for 12 X-linked disease loci as well as 10 DNA probes are excluded from the deleted area, and localized either proximally or distally to the deletion. The results also reveal a controversy in the present linkage data concerning the assignment of these loci.

Abnormalities, Multiple↗

Evaluation of the equivocal test results of Treponema pallidum haemagglutination assay.

Two hundred and eighty Rapid Plasma Reagin (RPR) positive sera with an emphasis on cases with negative and borderline positive Treponema pallidum haemagglutination assay (TPHA) results were selected. Modified TPHA (M-TPHA) and fluorescent treponemal antibody absorption (FTA-abs) tests were used for comparison. One hundred and twenty five samples were TPHA negative, of which 78 and 69 cases were also negative by M-TPHA and FTA-abs, respectively. Eighty one sera negative by TPHA at a titre of 1/80 and positive at 1/40, considered to be negative according to the manufacturer's instructions, were also negative by M-TPHA (n = 11) and by FTA-abs (n = 1). Fifty borderline positive TPHA specimens gave one negative result by both M-TPHA and FTA-abs. The remaining 24 sera were positive by all three tests. Because of the high percentage of TPHA negative results among the positive RPR sera which became reactive when rechecked by the FTA-abs, it is concluded that as a confirmatory test the TPHA should be used not instead of but in addition to the FTA-abs.

Antibodies, Bacterial↗

Chronic effects of a physiological dose of ANP on arterial pressure and renin release.

To determine the long-term effects of a physiological dose of atrial natriuretic peptide (ANP) on renin release, the renin response to reductions in renal arterial pressure (RAP) was studied during 1) control conditions and 2) acute and 3) chronic (5 days) intravenous infusion (5 ng.kg-1.min-1) of alpha-human ANP in conscious dogs maintained on a normal sodium intake. Renal perfusion pressure was servo controlled at reduced levels with an inflatable occluder placed around the abdominal aorta just above the renal arteries. Under control conditions, reducing RAP by 30 and 40 mmHg increased plasma renin activity (PRA) 4- to 5- and 9- to 10-fold, respectively. Acute ANP infusion had no significant effect on either basal levels of PRA or the PRA response to reduced RAP. During chronic ANP infusion there was a two- to threefold increment in plasma ANP concentration and approximately a twofold increase in urinary sodium excretion on day 1; however, there were no significant long-term changes in mean arterial pressure, basal PRA, or the levels of PRA achieved during reductions in RAP. These findings indicate that the changes in plasma ANP concentration that occur under normal physiological conditions do not appreciably alter either basal PRA or renin release in response to renal hypotension in conscious sodium-replete dogs studied under resting conditions.

Animals↗

Zygosity in two cases of triplet.

A total of 11 techniques including 57 items for zygosity diagnosis was employed in two sets of triplet. Namely, placenta-fetal membrane, LDH isoenzymes, etc. The authors made an investigation in detail on the pedigree history of polyembryony and systematic analysis of two sets of male triplets. The conclusion was that the first triplet came from a single ovum, whereas the second triplet developed from double ova. Different methods for the zygosity diagnosis were discussed. It was considered that there was hereditary influence in the occurrence of triplets developing either from a single ovum or from multiple ova.

Adult↗

Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18.

A complete family of IgG isotype switch variant hybridomas was generated from the anti-GD2 monoclonal IgG3-producing hybridoma, 14.18, with the aid of the fluorescence-activated cell sorter. The IgG1, IgG2b, and IgG2a monoclonal antibodies (Mabs) produced by respective isotype switch variant hybridomas 14G1, 14G2b, or 14G2a, have binding activities for the biochemically defined GD2 antigen and GD2-expressing neuroblastoma target cell lines identical to that of IgG3 Mabs produced by the 14.18 parent cell line. This permitted us to examine the relative in vitro and in vivo cytotoxic capacities of each of the anti-GD2 antibodies for GD2-expressing neuroblastoma cells independent of antibody binding affinity or specificity. Mabs produced by 14.18, 14G2a, or 14G2b, but not 14G1, can direct efficient complement-dependent cytotoxicity against neuroblastoma tumor cells in the presence of human complement. Mabs produced by the parent 14.18 or by 14G2a are more efficient in directing antibody-dependent cell-mediated cytotoxicity than Mabs produced by 14G2b, and Mabs of 14G1 are inactive. However, despite these noted in vitro differences, antibodies produced by each member of this switch variant family suppress the growth of human neuroblastoma tumor cells in BALB/c athymic nu/nu mice. These studies suggest that a mechanism(s) other than Fc-directed complement-dependent cytotoxicity or antibody-dependent cell-mediated cytotoxicity may account for the in vivo antitumor effects of these particular antibodies.

Animals↗

Sustained increases in plasma epinephrine concentration do not modulate renin release.

We examined the relationship between plasma renin activity (PRA) and renal arterial pressure (RAP) during 1) control conditions, 2) acute, and 3) chronic intravenous epinephrine (EPI) infusion (125 ng.kg-1.min-1). In eight conscious uninephrectomized dogs maintained on a normal sodium intake, the renin stimulus-response curve (RSRC) was determined by a stepwise reduction in RAP with an inflatable occluder around the renal artery controlled by a servo unit. The RSRC could be approximated by two lines intersecting at a threshold pressure (approximately 20 mmHg below control RAP). In the high-pressure range, PRA was relatively insensitive to changes in RAP, whereas, below threshold pressure, changes in RAP had large effects on PRA. During acute EPI infusion there was approximately a 40% increase in heart rate (control = 57 +/- 3 beats/min) and hematocrit (control = 30 +/- 1%) in association with a rise in plasma EPI concentration from 73 +/- 16 to 1,413 +/- 100 pg/ml; mean arterial pressure (MAP) was unchanged (94 +/- 3 mmHg). Moreover, EPI acutely increased basal PRA from 0.3 +/- 0.1 to 0.8 +/- 0.3 ng angiotensin I.ml-1.h-1 and shifted the RSRC to the right (increasing threshold pressure 7 mmHg) without altering the slope of the RSRC curve either above or below threshold pressure. In contrast, although plasma EPI concentration and hematocrit remained elevated during chronic EPI infusion, heart rate and basal PRA returned to preinfusion values. In addition, there were no significant long-term changes in MAP or in any of the parameters of the RSRC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacokinetics and mechanism of action of a doxorubicin-monoclonal antibody 9.2.27 conjugate directed to a human melanoma proteoglycan.

Doxorubicin (DXR) conjugated to a monoclonal antibody (MAb), 9.2.27, which recognizes a human melanoma-associated proteoglycan, effectively suppresses the growth of human melanoma xenografts and prolongs the life span of tumor-bearing athymic nude (nu/nu) mice. We have investigated further the mechanism(s) of this in vivo antitumor activity. Our results indicate that following iv injection, the DXR-MAb 9.2.27 conjugate is cleared from the circulation with typical biphasic kinetics, similar to the clearance process of the unconjugated MAb 9.2.27. In contrast, less than 10% of injected dose per milliliter of blood is found in the circulation at any given time after ip injection. Toxicity studies further indicate that DXR-MAb 9.2.27 conjugate is less toxic in vivo than the freely administered DXR, which is known to cause considerable cardiotoxic effects. Direct autoradiography demonstrates that the DXR-MAb 9.2.27 conjugate binds specifically to the tissue sections derived from a human melanoma xenograft of a nude mouse. A critical evaluation is given of the relevance of these findings and their impact on the design of future strategies for the immunochemotherapy of malignant melanoma.

Animals↗

Biochemical characterization of a sulfated phosphoglycoprotein antigen expressed on human small cell lung carcinoma.

A murine monoclonal antibody (mAb A23-16) was produced that recognizes a glycoprotein antigen preferentially expressed on the surface of human small cell lung carcinoma cells. This antibody is of IgG 1 isotype, has an association constant of 5 x 10(7) M-1, and reacts preferentially with human small cell lung carcinoma cell lines and fresh frozen sections in enzyme-linked immunosorbent assays and immunoperoxidase assays, respectively. The antigen recognized by A23-16 is a sulfated glycoprotein with phosphorylated threonine residues. The mature 90-kDa molecule has intrachain disulfide bonds and appears to be derived from a 76-kDa precursor, that is neither sulfated nor phosphorylated, but contains N-linked oligosaccharides. Conversion of the 76-kDa precursor to the mature form is accompanied by processing of these oligosaccharides from the high mannose to the complex type, although the increase in molecular mass from 76 to 90 kDa cannot be accounted for by this modification alone. MAb A23-16 reacts with its target antigen independent of the N-linked oligosaccharides, but requires intact intrachain disulfide bond(s) for reactivity. These studies on the molecular characterization of a monoclonal antibody-defined glycoprotein, preferentially expressed by small cell lung cancer, provide a basis for further structural and functional studies that may eventually lead to a delineation of its biological relevance for neoplastic transformation.

Adult↗

Regional localization of polymorphic DNA loci on the proximal long arm of the X chromosome using deletions associated with choroideremia.

In two unrelated families, males have been identified who suffer from choroideremia and at the same time have an interstitial deletion on the proximal long arm of the X chromosome. By high-resolution banding we have characterized the deletion chromosomes as del(X)(q21.1-q21.33) and del(X)(q21.2-q21.31) respectively. By Southern blot analysis we have mapped ten different polymorphic DNA loci relative to the position of the deletion and the choroideremia locus TCD. One probe, p31, was shown to cover one of the breakpoints of the smallest deletion. The following order of the loci was suggested by deletion mapping: cen-DXS106-DXS72-TCD-(DXYS1/DXYS23/DXYS5)- DXYS2-(DXYS12/DXS3)-(DXS17/DXS101)- Xqter.

Choroid↗

Doxorubicin conjugated with a monoclonal antibody directed to a human melanoma-associated proteoglycan suppresses the growth of established tumor xenografts in nude mice.

Doxorubicin (DXR) was covalently conjugated to a monoclonal antibody (mAb), 9.2.27 (IgG2a), which recognizes a chondroitin sulfate proteoglycan expressed preferentially on the surface of human melanoma cells. Immunoconjugates with a molar ratio of DXR to mAb ranging from 2:1 to 10:1 were obtained by coupling the drug via an acid-sensitive linker, cis-aconitic anhydride. The immunoreactivity of mAb 9.2.27 was well retained after conjugation. DXR-mAb 9.2.27 conjugates were found to be 2 orders of magnitude more potent in killing tumor cells in vitro (IC50 = 0.1 microM) than free drug targeted to drug receptor(s). Most significantly, DXR-mAb 9.2.27 immunoconjugates specifically suppressed the growth of established tumors in vivo and prolonged the life-span of tumor-bearing nude mice. This suppression of melanoma growth achieved by the immunoconjugate was both tumor and antibody specific. A biodistribution study indicated that DXR-mAb 9.2.27 conjugates delivered at least 4 times more DXR (3.7% total injected dose per g of tumor) as compared to free DXR alone (0.8% total injected dose per g of tumor) in tumor-bearing nude mice 48 hr postinjection. The tumor-suppressive effects of DXR-mAb 9.2.27 conjugates are even more remarkable since free DXR did not suppress tumor growth in vivo and also because this drug per se is known to be quite ineffective for the treatment of human melanoma.

Adenocarcinoma↗