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Biomedical subjects

H Yang

Publications and source records attributed to H Yang.

At least 1,009 records · Page 56Linked to original sources

A correlation study on urinary excretion of N-nitroso compounds and cancer mortality in China: interim results.

Samples of 12-h overnight urine were collected from approximately 40 male adults in each of the 26 counties of China. Two urine specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids, nitrite and nitrate were measured in urine samples and correlated with cancer mortality per 100,000 male subjects in the truncated age range 35-64 years. Preliminary results show no clear correlation between presence of stomach cancer or liver cancer and nitrosation potential [as measured by the urinary level of N-nitrosoproline (NPRO) after the proline load test or of nitrate]. There was a moderate, although not clearly significant, tendency for oesophageal cancer mortality rates to be associated positively with nitrosation potential and negatively with background ascorbate levels in plasma. This result was due chiefly to the inclusion of one county (Song Xian) in which there is a fairly high oesophageal mortality rate, an average nitrosation potential three times greater than that of any other county, and the lowest ascorbate index of any county. Further study of this county is planned.

Adult↗

Induction of alloreactive cytotoxic T cells by acute virus infection of mice.

Alloreactive cytotoxic T lymphocytes (CTL) distinct from virus-specific CTL and activated natural killer (NK) cells were generated during acute lymphocytic choriomeningitis virus (LCMV) infection of C57BL/6J mice. The alloreactive CTL shared similar antigenic markers (Thy-1.2+, Lyt-2.2+, and asialo GM1-) with the virus-specific CTL that appeared at the same time 7 days postinfection, but had different target specificities. These alloreactive CTL lysed allogeneic but not syngeneic or xenogeneic targets. These were distinct from activated NK cells, which lysed all target cell types, peaked 3 days postinfection, and had a phenotype of asialo GM1+, Thy-1 +/-, Lyt-2.2-. Cold target competition studies indicated that there were several subsets of alloreactive T cells with distinct specificities, and that these alloreactive T cells were not subsets of the virus-specific T cells. Similar types of alloreactive CTL were induced at much lower levels in C3H/St mice. This may indicate that the generation of this "aberrant" T cell activity is under genetic control. Hence, the LCMV infection of C57BL/6J mice induces several cytotoxic effector populations including alloreactive CTL, activated NK cells, and virus-specific CTL. Virus infections therefore have the ability not only to polyclonally stimulate B cells, as previously described, but also to stimulate CTL.

Acute Disease↗

Escherichia coli pyruvate dehydrogenase complex: particle masses of the complex and component enzymes measured by scanning transmission electron microscopy.

Particle masses of the Escherichia coli pyruvate dehydrogenase (PDH) complex and its component enzymes have been measured by scanning transmission electron microscopy (STEM). The particle mass of PDH complex measured by STEM is 5.28 X 10(6) with a standard deviation of 0.40 X 10(6). The masses of the component enzymes together with their standard deviations are (2.06 +/- 0.26) X 10(5) for the dimeric pyruvate dehydrogenase (E1), (1.15 +/- 0.17) X 10(5) for dimeric dihydrolipoyl dehydrogenase (E3), and (2.20 +/- 0.17) X 10(6) for dihydrolipoyl transacetylase (E2), the 24-subunit core enzyme. The latter value corresponds to a subunit molecular weight of (9.17 +/- 0.71) X 10(4) for E2. The subunit molecular weight measured by polyacrylamide gel electrophoresis in sodium dodecyl sulfate is 8.6 X 10(4). STEM measurements on PDH complex incubated with excess E3 or E1 failed to detect any additional binding of E3 but showed that the complex would bind additional E1 under forcing conditions (high concentrations with glutaraldehyde). The additional E1 subunits were bound too weakly to represent binding sites in an isolated or isolable complex. The mass measurements by STEM are consistent with the subunit composition 24:24:12 when interpreted in the light of the flavin content of the complex and assuming 24 subunits in the core enzyme (E2).

Acetyltransferases↗

T cell-dependent and -independent stimulation of hamster spleen NK-like cells with concanavalin A.

This study was designed to examine the inducibility and lineage of nonspecifically cytotoxic effector cells in the hamster spleen. Employing a known T cell mitogen, concanavalin A (ConA), and a monoclonal antibody against a recently identified hamster T cell marker (Thy 1.2 homologue), we examined the effector cells induced in spleen by ConA and the role of T cells in regulating this response. Cytotoxicity was measured against uninfected baby hamster kidney cells, cells infected with herpes simplex virus, or a mouse target, SV3T3, in a 16-hr 51Cr release assay. Pretreatment of spleen cells with ConA (2.5-10 micrograms ConA/ml) markedly augmented killing of all targets. Although ConA pretreatment of effector cells enhanced cytotoxicity, pretreatment of targets did not, indicating that ConA is acting at the effector cell level. Supernatants from ConA-stimulated spleen cells also augmented spleen lymphocyte cytotoxicity, suggesting that the ConA effect is mediated by lymphokines (LK). Depletion of Thy 1.2-positive cells from the spleen cells failed to influence augmentation of cytotoxicity by either ConA or ConA-induced LK, indicating that the precursor cells are not T cells. However, depletion of Thy 1.2-positive cells completely eliminated the production of LK in response to ConA, indicating that the factors in LK that augment cytotoxicity are strictly T cell dependent. Whether nonspecific cytotoxic cells induced by ConA in the absence of T cells and by the T cell LK are the same population is not known. None of the cytotoxicity induced from intact or T cell-depleted spleen cells by either ConA or LK expressed the Thy 1.2 homologue. These results suggest that nonspecific cytotoxic lymphocytes of non-T cell lineage in the hamster are regulated via both T cell-dependent and T cell-independent mechanisms.

Animals↗

The isolation and partial characterization of a highly pathogenic herpesvirus from the harbor seal (Phoca vitulina).

This report describes the first isolation and partial characterization of a herpesvirus from the harbor seal (Phoca vitulina). The virus was isolated during a disease outbreak in a group of young seals nursed in a seal orphanage in The Netherlands. Almost half of the seals died with symptoms of acute pneumonia and focal hepatitis and the virus was isolated of organs of most of the dead animals. Seven out of ten seals of which paired serum samples were obtained showed seroconversion in a virus neutralization test during this outbreak. The virus was tentatively characterized as a herpesvirus (seal herpesvirus: SeHV or phocid herpesvirus 1) on the basis of its characteristic morphology in electron microscopy, buoyant density in sucrose, sensitivity to ether and heat treatment and its antigenic relationship with other probable members of the Alphaherpesvirinae subfamily. The virus caused cytopathic changes within 24 hours after inoculation in seal kidney cells, consisting of a focal rounding of cells and syncytium formation. No cytopathic changes were observed in the cells of nine other mammalian species tested.

Animals↗

Expression of asialo GM1 and other antigens and glycolipids on natural killer cells and spleen leukocytes in virus-infected mice.

The sensitivities of mouse natural killer (NK) cells to various antisera and complement were analyzed at different time points after acute lymphocytic choriomeningitis virus infection. Under these conditions NK cell activity peaks 3 days and virus-specific cytotoxic T cell activity 7 days after infection. The sensitivity of the cytotoxic activities to antibodies to asialo GM1 (AGM1), NK 1.2 alloantigen, and Ly 5 was in the order endogenous NK greater than day 3 NK greater than day 7 NK. Day 7 cytotoxic T cells were more resistant than day 7 NK to anti-AGM1 and to anti-NK 1.2, but more sensitive to anti-Ly 5. This decreased sensitivity of activated NK cells to antibodies and C' was examined in more detail for the AGM1 antigen. Antibody to AGM1 completely depleted NK cell activity in control, but not in day 3 lymphocytic choriomeningitis virus infected mice. However, mice treated before infection with antibody did not generate NK cell activity 3 days after infection. The mechanisms of the decreased sensitivity of activated NK cells to antibody to AGM1 was examined. High levels of antibody depleted activity, indicating that the effectors were not devoid of AGM1. Biochemical analyses of spleen leukocytes revealed marked increases in sialic acid, gangliosides, and neutral glycosphingolipids, including AGM1 in the order day 7 greater than day 3 greater than endogenous. Antibody to AGM1 was absorbed out by leukocytes in the order day 7 greater than day 3 greater than endogenous. Flow cytometry (FACS) analyses revealed marked shifts in the frequency and intensity of staining of cells with antibody to AGM1 in the order day 7 greater than day 3 greater than endogenous. All endogenous NK cell activity and all the large granular lymphocytes were associated with the brightest 5% of the total spleen leukocyte population. Day 3 and day 7 NK cell activity was also located in cells sorted by using the gate settings for the top 5% endogenous cells. However, there were marked increases in the number of the very bright cells in the order day 3 greater than day 7 greater than endogenous. These cell numbers correlate with the level of NK cell activity in these fractions. Thus, the decreased sensitivity of activated NK cells to antibody to AGM1 is not due to decreased expression of AGM1 on NK cells, but to a competition for antibody by greatly increased levels of AGM1 in infected spleen leukocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Synthesis of undecagold cluster molecules as biochemical labeling reagents. 2. Bromoacetyl and maleimido undecagold clusters.

Derivatives of heptakis[4,4',4"-phosphinidynetris(benzenemethanamine) ]undecagold, 1, molecular formula Au11(CN)3[P(C6H4CH2NH3)]7, are described. These include undecagold complexes with a single free primary amino group, a single bromoacetyl group, and a single maleimido group per molecule. Hydrolysis of mono(N-phthalyl)icosa(N-acetyl)-1 at pH 3.2 and 46 degrees C under anaerobic conditions and in the presence of NaBH3CN produces icosa(N-acetyl)-1. Partial acylation of 1 with 1.3 equiv of 2,3-dimethylmaleic anhydride followed by complete acetylation with acetic anhydride produces a mixture consisting largely of mono- and bis(dimethylmaleyl)peracetyl-1. Hydrolysis of 2,3-dimethylmaleimides at pH 3.2 for 1 at 25 degrees C produces a mixture of icosa(N-acetyl)-1, with a single free amino group, and nondea(N-acetyl)-1. This mixture can be quantitatively separated by cation-exchange chromatography at pH 7, giving homogeneous icosa(N-acetyl)-1 in an overall yield of 55%. Icosa(N-acetyl)-1 serves as the starting material for the synthesis of the alkylating derivatives mono(N-bromoacetyl)icosa(N-acetyl)-1 and mono[N-(p-maleimidobenzoyl)]icosa(N-acetyl)-1. These derivatives can be used for alkylating proteins in preparation for electron microscopy.

Acetates↗

Synthesis of undecagold cluster molecules as biochemical labeling reagents. 3. Dimeric cluster with a single reactive amino group.

The synthesis and characterization of a dimeric derivative of the undecagold cluster complex Au11(CN)3[P-(C6H4CH2NH2)3]7, 1, are described. The dimer, 2, consists of cross-linked molecules of 1 in which 41 of the 42 amino groups are acylated, leaving a single free amino group per dimer. This amino group is reactive and can be used to prepare derivatives of 2 for use in labeling biological macromolecules in preparation for electron microscopic analysis. Limited acylation of 1 by 1.3 equiv of citraconic anhydride in aqueous solution, followed by extensive acylation with acetic anhydride at pH 7-7.5, leads to a mixture of monomeric and dimeric products. Hydrolytic removal of N-citraconyl groups at pH 3.2 unmasks a few amino groups. Cation-exchange chromatography at pH 7 separates the products into three main groups, species containing one, two, or three free amino groups, in overall yields of 33%, 28%, and 15%, respectively. The monoamino species consist mainly of 2 and a monomeric product, which are separated by gel exclusion chromatography. 2 migrates as a dimer upon polyacrylamide gel electrophoresis in sodium dodecyl sulfate, and it contains a single free amino group, detectable by its ion-exchange behavior as a monocation at pH 7 and by its reactivity with [14C]phthalic anhydride.

Chemical Phenomena↗

The incidence of hypercalcemia in squamous cell carcinoma of the head and neck.

Hypercalcemia is a well-recognized phenomenon in squamous cell carcinoma of the head and neck, but the incidence of hypercalcemia in this group of patients is not clear. We have reviewed the records of 166 patients with squamous cell carcinoma of the head and neck presented at the Boston VA Medical Center over a 2-year period (October 1981 to September 1983). Hypercalcemia (greater than 11 mg/dl), for which a benign etiology could not be identified, occurred in the clinical course of seven patients (4.2%). Of the hypercalcemic patients, 5/7 (71.4%) had advanced stage IV disease and serum calcium levels ranging from 11.2 to 15 mg/dl at presentation. The incidence of hypercalcemia in this stage IV group was 5/78 (6.4%). On the basis of concomitant serum alkaline phosphatase, x-ray films, and radionuclide bone scans in these patients, bone metastases or a humoral factor were felt to be the etiologic agent. Six of the seven patients died within 77 days of the onset of the hypercalcemia despite vigorous antihypercalcemic and chemotherapeutic measures, and the remaining patient is under chemotherapy at present. We conclude that hypercalcemia is a late manifestation of advanced squamous cell carcinoma of the head and neck and is an ominous prognostic sign. Hypercalcemia without bone metastases is presumably due to the production of ectopic parathormone (PTH)-like substances from the tumor. To control this hypercalcemia, the underlying tumor must be treated vigorously in conjunction with symptomatic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗