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Biomedical subjects

J Tang

Publications and source records attributed to J Tang.

At least 523 records · Page 29Linked to original sources

[Atrial natriuretic polypeptide in the human and rat spinal cord].

The widespread distribution of atrial natriuretic polypeptide (ANP) immunoreactive material was demonstrated in the human and rat spinal cord, using specific immunogold-silver staining technique and radioimmunoassay. Immunogold-silver staining studies showed that ANP immunoreactive neurons were quite prevalent in the human spinal cord. ANP immunoreactive neurons were largely found in the ventral horn and less in the dorsal and lateral horns. ANP immunoreactive material was absent with anti-ANP serum preabsorbed with ANP. In rats, radioimmunoassay demonstrated that ANP immunoreactive material was present in whole spinal cord. The highest concentration was found in the sacral spinal cord (21.9 +/- 4.48 ng/g tissue), the moderate in the lumbar (3.78 +/- 0.74 ng/g tissue) and the lowest in the cervical and thoracic (0.58 +/- 0.14 and 0.46 +/- 0.21 ng/g tissue, respectively). Gel chromatography and reverse-phase HPLC revealed multiple molecular forms in the rat spinal cord, but the main molecular form was the 28 amino acid rANP. In vivo study showed that ANP was released from the rat spinal cord by depolarizing concentration of potassium.

Animals↗

[Effects of human atrial natriuretic factor-(99-126) on plasma and brain vasopressin in stroke-prone spontaneously hypertensive rats].

In order to investigate the interaction between atrial natriuretic factor (ANF) and arginine vasopressin (AVP) in the pathogenesis of essential hypertension, the effects of intravenous (iv) or intracerebroventricular (icv) injection of human ANF-(99-126) on plasma and brain AVP, as well as mean arterial pressure (MAP), urinary volume (UV) and sodium (UNaV) excretion in stroke-prone spontaneously hypertensive rats (SHRsp) and age-matched normotensive Wistar-Kyoto rats (WKY) were studied. The results showed that ten minutes after iv injection of ANF, MAP decreased by 9.4% and 12.2% (P less than 0.05), UV increased about 9 and 20 folds (P less than 0.01), UNaV increased about 16 and 29 folds (P less than 0.01) in SHRsp and WKY rats, respectively. No such significant changes in these parameters were found in the icv group. Although iv and icv injection of ANF caused significant decrease of plasma AVP in both strains, the decrease was less marked in SHRsp than in WKY rats, while the maximum decreases were 58% (iv) and 31% (icv) in SHRsp, the corresponding values were 80% (iv) and 65% (icv) in WKY. Intravenous and intracerebroventricular injection of ANF also induced significant increase of hypothalamic AVP in both SHRsp and WKY rats, but no significant change could be found in hypophyseal AVP content. The results suggest that decreased sensitivity of AVP inhibition as well as less marked hypotensive, diuretic and natriuretic effects to ANF in SHRsp might play a role in the pathogenesis of their hypertension.

Animals↗

[Significance of endothelin in shock pathogenesis].

Endothelin is a recently discovered bioactive peptide produced by vascular endothelial cells. By means of specific radioimmunoassay we found that plasma endothelin level in patients with late septic shock was significantly increased. And a typical shock model in healthy rats was reproduced by continuous infusion of endothelin (endothelin shock). Infusion of endothelin at a small dose to hemorrhagic shocked rats deteriorated the shock process and resulted in an irreversible development. From these results it is suggested that endothelin may be an endogenous injury-inducing factor, acting as one of the important humoral factors involved in shock pathogenesis.

Animals↗

Structures at the proteolytic processing region of cathepsin D.

The amino acid sequences at the "proteolytic processing regions" of cathepsin Ds have been determined for the enzymes from cows, pigs, and rats in order to deduce the sites of cleavage as well as the function of the proteolytic processing of cathepsin D. For bovine cathepsin D, the "processing region" sequence was determined from a peptide isolated from the single-chain enzyme. The COOH-terminal sequence of the light chain and the NH2-terminal sequence of the heavy chain were also determined. The processing region sequence of porcine cathepsin D was determined from its cDNA structure, and the same structure from rat cathepsin D was determined from the peptide sequence of the single-chain rat enzyme. From sequence homology to other aspartic proteases whose x-ray crystallographic structures are known, such as pepsinogen and penicillopepsin, it is clear that the processing regions are insertions to form an extended beta-hairpin loop between residues 91 and 92 (porcine pepsin numbers). However, the sizes of the processing regions of cathepsin Ds from different species are considerably different. For the enzymes from rats, cows, pigs, and human, the sizes of the processing regions are 6, 9, 9, and 11 amino acid residues, respectively. The amino acid sequences within the processing regions are considerably different. In addition, the proteolytic processing sites were found to be completely different in the bovine and porcine cathepsin Ds. While in the porcine enzyme, an Asn-Ser bond and a Gly-Val bond are cleaved to release 5 residues as a consequence of the processing; in the bovine enzyme, two Ser-Ser bonds are cleaved to release 2 serine residues. These findings would argue that the in vivo proteolytic processing of the cathepsin D single chain is probably not carried out by a specific "processing protease." Model building of the cathepsin D processing region conformation was conducted utilizing the homology between procathepsin D and porcine pepsinogen. The beta-hairpin structure of the processing region was found to (i) interact with the activation peptide of the procathepsin D in a beta-structure and (ii) place the Cys residue in the processing region within disulfide linkage distance to Cys-27 of cathepsin D light chain. These observations support the view that the processing region of cathepsin D may function to stabilize the conformation of procathepsin D and may play a role in its activation.

Amino Acid Sequence↗

In vivo effects of recombinant human interleukin 2 on antitumor and antiviral natural immunity in induced or natural murine immunodeficiency states.

We have examined the ability of in vivo treatment of mice with recombinant interleukin 2 (rIL-2) to affect natural immunity measured against tumor (YAC-1) or virally infected (herpes simplex type 1) target cells. rIL-2 treatment leads to significant increases in natural killer/lymphocyte-activated killer (NK/LAK) function and spleen cells recovered. This effect is dose dependent and strain related. The latter parameter correlated with the pretreatment NK activity level of the strain. The rIL-2 induced NK/LAK augmentation is also kinetically restricted as treatment must have occurred within 48-72 h of assay to be effective. The rIL-2 therapy effectively enhances both antitumor and antiviral NK/LAK activity and results in a noticeable increase in asialo-GM1-positive cells in the spleens of treated mice as well as a significant increase in IL-2 receptor expression as monitored by either cytometry or radioligand binding. In vivo treatment of mice with an antibody directed to the ASGM1 determinant effectively reduces the rIL-2 augmentation of both antitumor and antiviral activity even though this treatment does not affect the pretreatment level of antiviral activity. Various natural and induced immunodeficiency states (immunotherapy, irradiation, immunosuppressive drugs, cytoreductive drugs) have been examined for the ability of in vivo treatment with rIL-2 to enhance NK/LAK activity. In vivo rIL-2 administration is differentially effective in enhancing NK/LAK activity in these situations. Notably, in these induced immunodeficiency states, although NK/LAK activity is commonly enhanced, the number of spleen cells recovered often is only marginally affected. Thus, as expected, a limiting aspect in this use of a natural immunomodulator is the number of potentially responsive cells present in the immunodeficiency condition. In addition, correlations between rIL-2 effect, several of the immunodeficiency states, and vascular leak syndrome are briefly discussed.

Animals↗

Porcine spleen cathepsin H hydrolyzes oligopeptides solely by aminopeptidase activity.

Cathepsin H purified from porcine spleens was studied for its specificity against various peptide and denatured protein substrates. The enzyme degraded all peptide substrates exclusively by an aminopeptidase activity. The enzyme preferentially released NH2-terminal amino acid residues with large hydrophobic (Phe, Trp, Leu, and Tyr) or basic (Arg and Lys) side chains. Amino acids containing small or polar side chains were not released. Peptides with a proline in the NH2-terminal or penultimate positions were not hydrolyzed either. Large polypeptides such as reduced and carboxymethylated soybean trypsin inhibitor and aldolase were not degraded. These results indicate that cathepsin H is an exopeptidase but not an endopeptidase. We propose that the biological role of this enzyme is the degradation of tissue proteins in lysosomes by its aminopeptidase activity.

Amino Acid Sequence↗

A dynorphin peptide induces hypotension by stimulating the release of atrial natriuretic peptide from rat atrium.

Intravenous injection of dynorphin A-(1-10) amide (Dyn, 81-324 nmol/kg) induced a dose-dependent hypotensive effect in the rat. This effect was antagonized by pretreatment with immunoglobulin G, purified from a specific antiserum raised against alpha-human atrial natriuretic peptide (anti-hANP-IgG), as well as by high doses of naloxone (2 or 10 mg/kg). In addition, a 12-fold increase in plasma level of atrial natriuretic peptide-like immunoreactivity (ANP-IR) was found following Dyn administration, which was accompanied by a significant decrease of atrial ANP-IR. These results suggest that the stimulated release of ANP-IR from the atrium may constitute one of the mechanisms for the depressor effect of dynorphin peptides.

Animals↗

[Alpha-hANP-like immunoreactivity in lung cancer].

Specific radioimmunoassay and immunohistochemical method of alpha-human atrial natriuretic polypeptide (alpha-hANP) was established to diagnose one case of large cell lung carcinoma (clear cell carcinoma) proved by pathology. It was found that there was alpha-hANP-like immunoreactivity in the cancer cells at a concentration of 147.5 pg/mg protein. Chromatography analysis showed that alpha-hANP-like immunoreactive materials had multiple molecular forms. The significance of these phenomena remains to be further investigated.

Adenocarcinoma↗

Synergistic effect of granulocyte-macrophage colony-stimulating factor and 1,25-dihydroxyvitamin D3 on the differentiation of the human monocytic cell line U937.

The human monoblastlike cell line U937 can be induced to differentiate by a variety of agents including gamma-interferon, phorbol esters, retinoic acid, and 1,25-dihydroxyvitamin D3 (VD3). Incubation of U937 with 1 to 1,000 units of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) did not induce macrophage differentiation. A synergistic effect on macrophage differentiation was observed, however, when U937 was cocultured with 10(-8) mol/L VD3 plus 50 U/mL GM-CSF. GM-CSF-plus VD3-treated cells demonstrated significant increases in OKM1 antigen expression, increased chemokinesis and chemotaxis, and increased Fc receptor-mediated erythrophagocytosis. Human peripheral blood monocyte cultures also demonstrated increased OKM1 antigen expression and chemotaxis when incubated with 50 to 500 U/mL of GM-CSF for 48 to 72 hours. VD3, however, was not necessary for the increases in effector function observed for GM-CSF-stimulated monocyte cultures. In distinction to the synergistic effect of GM-CSF on VD3-induced differentiation of U937, recombinant human granulocyte colony-stimulating factor (G-CSF) at comparable concentrations had no augmenting effect over that observed for VD3 alone. These results suggest that GM-CSF, in the presence of other physiological stimuli, can induce significant phenotypic changes in GM-CSF-nonresponsive cells of the monocytic lineage and can increase the effector functions of GM-CSF-responsive peripheral blood monocyte cultures.

Antigens, Surface↗

Therapeutic actions of alpha-human atrial natriuretic polypeptide in 16 clinical cases.

Alpha-human atrial natriuretic polypeptide (alpha-hANP) was applied to 16 clinical patients, 6 patients with essential hypertension, 7 patients with congestive heart failure and 3 patients with cirrhosis. Following intravenous bolus injection of 400 micrograms of synthetic alpha-hANP, a hypotensive effect of very rapid onset was found, which was more potent in the hypertensive patients than in the normotensive cases. Cardiac functions were improved significantly with a similar time course as the depressor response in the cases of heart failure or hypertension. Hemodynamic observations showed a marked increase in cardiac output, cardiac index, stroke volume, ejection fraction and ejection rate, and a concomitant decrease of the pressure in the right side of the heart and pulmonary circulation in these subjects. In addition, the renal response to alpha-hANP induced obvious increases in urine volume, electrolytes and creatinine excretions in all the subjects. Finally, plasma levels of aldosterone, Arg-vasopressin and noradrenaline were also altered by alpha-hANP. No significant side effects were registered. The above result confirms the therapeutic actions of alpha-hANP in human subjects and opens the possibility to research alpha-hANP as a powerful pharmacological tool as well as potential new medicine for human disorders.

Adult↗

Amino acid sequence of rhizopuspepsin isozyme pI 5.

The complete amino acid sequence of an aspartic protease from Rhizopus chinensis, rhizopuspepsin isozyme pI 5, has been determined. Partial sequences were first obtained from the isolated isozyme by a combination of chemical and proteolytic enzyme cleavages, peptide purifications, and Edman degradations. About one-half of the sequence was revealed by this approach. To complete the amino acid sequence, a cDNA library of R. chinensis in pBR322 was constructed. An oligonucleotide probe was synthesized based on the sequence Trp-Trp-Gly-Ile-Thr, and about 40 positive clones were identified by colony hybridization. A clone, 33E2, which had an insert size of about 1.1 kilobase pairs, was found to contain the entire coding region of rhizopuspepsin isozyme pI 5. The sequence of rhizopuspepsin contains 325 amino acid residues. The alignment of the rhizopuspepsin sequence against other aspartic proteases revealed expected homology, with the closest similarity to penicillopepsin which shares 39% identical residues. Porcine pepsin shares about 36% identical residues with rhizopuspepsin.

Amino Acid Sequence↗