Search PubMed⌕ Search

Biomedical subjects

M Huang

Publications and source records attributed to M Huang.

392 records · Page 22Linked to original sources

The biogenesis of mitochondria. II. The influence of medium composition on the cytology of anaerobically grown Saccharomyces cerevisiae.

Yeast cells grown anaerobically have been shown to vary in their ultrastructure and absorption spectrum depending upon the composition of the growth medium. The changes observed in the anaerobically grown cells are governed by the availability of unsaturated fatty acids and ergosterol and a catabolite or glucose repression. All the cells contain nuclear and plasma membranes, but the extent of the occurrence of vacuolar and mitochondrial membranes varies greatly with the growth conditions. Cells grown anaerobically on the least nutritive medium, composed of 0.5% Difco yeast extract-5% glucose-inorganic salts (YE-G), appear to contain little vacuolar membrane and no clearly recognizable mitochondrial profiles. Cells grown anaerobically on the YE-G medium supplemented with Tween 80 and ergosterol contain clearly recognizable vacuolar membrane and some mitochondrial profiles, albeit rather poorly defined. Cells grown on YE-G medium supplemented only with Tween 80 are characterized by the presence of large amounts of cytoplasmic membrane in addition to vacuolar membrane and perhaps some primitive mitochondrial profiles. When galactose replaces glucose as the major carbon source in the medium, the mitochondrial profiles within the cytoplasm become more clearly recognizable and their number increases. In aerobically grown cells, the catabolite repression also operates to reduce the total number of mitochondrial profiles. The possibility is discussed that cells grown anaerobically on the YE-G medium may not contain mitochondrial membrane and, therefore, that such cells, on aeration, form mitochondrial membrane from nonmitochondrial sources. A wide variety of absorption compounds is observed in anaerobically grown cells which do not correspond to any of the classical aerobic yeast cytochromes. The number and relative proportions of these anaerobic compounds depend upon the composition of the growth medium, the most complex spectrum being found in cells grown in the absence of lipid supplements.

Cell Membrane↗

Ventricular arrhythmia associated with respiratory syncytial viral infection.

Respiratory syncytial virus (RSV) is a common cause of lower respiratory infections in infants. Cardiac arrhythmias are an uncommon complication in infants with RSV bronchiolitis. Presumably, the arrhythmias may be secondary to RSV pericarditis, myocarditis, or some other infection of the heart. We report on a patient with RSV bronchiolitis who had clinical myocarditis complicated by ventricular tachycardia.

Bronchiolitis↗

Fetal obstructive uropathy: patterns of renal pathology.

Fetal obstructive uropathy (FOU) is characterized by obstruction of the urethra, renal anomalies, ureterovesical dilatation, oligohydramnios, cryptorchidism, and abdominal muscle wall changes. The main objective of the present study was to better understand the relationship between FOU and renal pathology using a series of 15 male autopsy cases. A total of 11 cases with patent anus and 4 with imperforate anus were analyzed. Of the first group, most cases showed obstruction at the level of prostatic urethra. Seven cases showed obstruction at the level of the prostatic urethra and histologic study revealed scarring and partial or complete absence of the prostate, while in the remaining four cases the prostate was present. Of the cases with imperforate anus, two showed obstruction at the level of prostatic urethra, one showed posterior urethral valves, and one was obstructed at the proximal urethra. In all cases the kidneys showed mixed (dysplastic and cystic) changes with no significant differences between the two groups. An inverse correlation was observed between degree of renal dysplasia and gestational age, whereas the opposite was true for cystic changes. Distal and collecting tubules were more intensely immunoreactive to the anti-cytokeratin antibody when compared to proximal tubules. Moreover, anti-cytokeratin immunoreactivity was more prominent in tubules displaying cystic dilatation. DNA fragmentation analysis of renal tissue revealed a higher apoptosis of mesenchymal and tubular cells in the FOU cases, compared to gestational aged-matched controls. These results suggest that renal anomalies in FOU might be related to the gestational age at which the injury occurred and to the duration of the obstruction.

Apoptosis↗

VIP receptors in mesenteric and coronary arteries: a radioligand binding study.

Using a biologically active radioligand, [Tyr(125I)10]VIP, we have identified and characterized receptors for vasoactive intestinal peptide (VIP) on membranes prepared from the rat superior mesenteric artery and bovine coronary arteries. Binding was specific, saturable, reversible and dependent on time and temperature. Scatchard analysis suggested the presence of a high and a low affinity binding site in each arterial system with the following binding constants: the rat mesenteric artery, KD = 0.22 +/- 0.02 and 13.6 +/- 7.8 nM (corresponding maximum number of binding sites, RO = 606 +/- 44 fmol/mg protein and 2.1 +/- 0.2 pmol/mg protein); bovine circumflex coronary artery, KD = 0.10 +/- 0.01 and 37.8 +/- 16.1 nM (corresponding RO = 369 +/- 65 fmol/mg protein and 2.0 +/- 0.7 pmol/mg protein); bovine left and right descending coronary arteries, KD = 0.12 +/- 0.03 and 21.3 +/- 6.4 nM (corresponding RO = 472 +/- 7 fmol/mg protein and 2.2 +/- 0.3 pmol/mg protein). The arterial VIP receptors did not recognize secretin, glucagon, apamin or bovine parathyroid hormone, and had reduced affinity for PHI, PHM and growth hormone releasing factors (GRF). These recognition properties were, by and large, similar to those seen in the bovine cerebral arteries although a between-species heterogeneity of recognition function could be deduced from the differences in the competitive binding of rat and bovine vascular VIP receptors with the corresponding species-specific GRFs.

Animals↗

Evidence that vascular actions of PHI are mediated by a VIP-preferring receptor.

Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are homologous neuropeptides which share vasodilatory properties. This paper addresses the question of whether PHI exerts its vascular action via a receptor distinct from that for VIP. Radioligand binding experiments were done using [Tyr(125I)10]VIP, [Tyr(125I)22]porcine PHI, [Tyr(125I)10]rat PHI and arterial preparations from rat, bovine and porcine species. The radioiodination of rat PHI by the lactoperoxidase-glucose oxidase method and analysis of the structure of the major radiolabeled derivatives were described. All the receptor binding experiments identified a VIP-preferring receptor irrespective of which radioligand or arterial preparation was utilized. VIP and PHI peptides demonstrated cross-desensitization in studies of relaxation of porcine coronary arterial strips in vitro. The present results favor the conclusion that the vascular actions of the PHI peptides are best explained by binding to a VIP-preferring receptor.

Amino Acid Sequence↗

PHI preferentially binds to VIP receptors in normal rat tissues.

Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are homologous neuropeptides with parallel biological actions. These similarities raise the question whether VIP and PHI have common or distinct mechanisms of action, including receptors. The present study attempted to distinguish specific binding sites for VIP and PHI in normal rat tissues using the homologous radioligands [Tyr(125I)10]VIP and [Tyr(125I)10]rat PHI. In rat brain, anterior pituitary, and liver membranes both radioligands identified a VIP-preferring receptor. Rat PHI had less than 10% the binding potency of VIP in these tissues irrespective of which radioligand was used. In rat uterine membranes [Tyr(125I)10]VIP bound to a receptor with approximately 100 times greater affinity for VIP over PHI. No specific binding of [Tyr(125I)10]rat PHI to rat uterus could be demonstrated. In conclusion, these results support the predominance of VIP-preferring receptors as opposed to PHI-preferring receptors in normal rat brain, anterior pituitary, liver and uterus.

Animals↗

Selective effect of castration on the anterior pituitary VIP receptor of male rats.

We investigated the effect of surgical castration of male rats on the binding of [Tyr(125I)10]VIP to receptors on the anterior pituitary gland, superior mesenteric artery, brain, liver, and prostate gland. In anterior pituitary membranes the maximum number of VIP binding sites was increased whereas binding affinity was decreased 24 hours following castration. In particular, the high affinity equilibrium dissociation constant (KD) increased from 0.13 +/- 0.02 nM (mean +/- SEM) to 0.67 +/- 0.07 nM and the maximum number of high affinity binding sites (Bmax) increased from 71 +/- 9 to 470 +/- 112 fmol/mg protein. No significant change was observed in the other tissues. Anesthesia or sham operation did not alter the anterior pituitary VIP receptor binding parameters. The changes in the VIP receptor 24 hours after castration were prevented by prior injection of testosterone. These findings demonstrate tissue-selective alterations to the anterior pituitary VIP receptor by castration that are likely mediated by withdrawal of testosterone.

Animals↗

Comparative study of vascular relaxation and receptor binding by PACAP and VIP.

The pharmacological properties of the pituitary adenylate cyclase activating peptides (PACAPs) and vasoactive intestinal peptide (VIP) were compared using: (i) relaxation of vascular and gastric smooth muscle in vitro, and (ii) radioligand binding to membrane preparations of a variety of tissues. Vasoactive intestinal peptide and PACAP-27 were similarly potent in relaxing rat mesenteric arteries, porcine coronary arteries, and rat gastric smooth muscle, whereas PACAP-38 was either more or less potent than the other two peptides depending on the tissue model. Cross-desensitization to relaxation and radioligand binding studies of porcine coronary arteries suggested that VIP and the PACAPs interact with a common receptor in this tissue. A PACAP-preferring receptor with low affinity for VIP was identified in radioligand binding studies of rat brain and anterior pituitary. A second, nonselective, receptor that binds VIP and both PACAPs with high affinity was observed in preparations of rat and porcine arteries and rat lung, liver, brain, and anterior pituitary.

Animals↗

Cadmium and lead interactions with transcription factor IIIA from Xenopus laevis: a model for zinc finger protein reactions with toxic metal ions and metallothionein.

Zinc finger proteins comprise the largest class of eukaryotic transcription factors. The metal binding sites in these proteins have been proposed as plausible targets for exchange reactions between zinc and toxic metal ions that lead to the alteration of function of the proteins in gene transcription. According to the present work, both Cd2+ and Pb2+ displace Zn2+ from transcription factor IIIA (TFIIIA). Neither product binds to the internal control region (ICR) of the 5 S rRNA gene, the normal binding site for Zn-TFIIIA. Furthermore, the adduct of Zn-TFIIIA with ICR is also reactive with Cd2+ and Pb2+, leading to the dissociation of the DNA-protein complex. Cd-TFIIIA reacts with apometallothionein (apoMT) to form Cd-MT and apoTFIIIA. Similarly, Cd2+ and Zn2+ can be exchanged in the reaction of Cd-TFIIIA with Zn-MT. Zn-finger 3 of TFIIIA has also been examined to compare the reactivity of a single finger motif with fingers in the holoprotein. Zn-finger 3 reacts with much faster kinetics than the holoprotein.

Animals↗

Effect of anti-cancer drugs on the binding of 125I-Fibrinogen to two leukaemia cell lines in vitro.

Anti-cancer drugs may be able to inhibit tumour growth and metastasis by blocking fibrinogen- and/or fibrin-related pathways. To test this hypothesis, the effect of various anti-neoplastic drugs on the binding of 125I-Fibrinogen to two leukaemia cell lines, HL60 and P388, was investigated. All the drugs tested inhibited the binding of fibrinogen to leukaemia cells. This effect was particularly marked for drugs that act as inhibitors of protein synthesis. Since these anti-neoplastic drugs do not have anti-coagulant actions, these results provide evidence for the potential of targeting tumour fibrinogen as a new form of cancer chemotherapy.

Antineoplastic Agents↗

Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis.

The AKT oncogenes are amplified or AKT kinase activity is constitutively elevated in several types of human malignancy. We sought to determine whether AKT might play a role in the development of resistance to apoptosis induced by chemotherapy. We showed that ovarian cancer cells either overexpressing constitutively active Akt/AKT1 or containing AKT2 gene amplification were highly resistant to paclitaxel than cancer cells express low AKT levels. The Akt/AKT1 clones also contained higher levels of phospho-Bad protein than parental cells. Further, the complexes between the endogenous proapoptotic protein, Bad, and the anti-apoptotic protein, BC1-XL were undetectable in Akt/AKT1 clones. These results suggest that Akt/AKT1 expressed in these clones can phosphorylate Bad and prevent it from binding to Bcl-XL. Furthermore, overexpression of Akt/AKT1 can inhibit the release of cytochrome c induced by paclitaxel. Therefore, our findings provide evidence that aberrant expression or activation of AKT in cancer cells may confer resistance to paclitaxel.

Adenocarcinoma↗

Interleukin-7 gene transfer in non-small-cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity.

Cytokine gene transfer to tumor cells can augment host antitumor responses and modify tumor phenotype. To evaluate the immunoregulatory and antitumor capacities of lung tumor-derived interleukin-7 (IL-7), we transduced non-small-cell lung cancer (NSCLC) cell lines with the IL-7/HyTK internal ribosomal entry site (IRES) retroviral vector and evaluated modifications in tumor phenotype and cocultured effector activities. In vitro proliferation of IL-7-transduced tumor cells was significantly less than control vector-transduced and parental tumor cells. The decreased proliferation rates of IL-7-transduced cells could be reproduced by adding high concentrations of recombinant IL-7 to the parental cells. Anti-IL-7 monoclonal antibody significantly increased the proliferation of the IL-7-transduced cells (P < .05). Parental NSCLC cells were found to express the IL-7 receptor, and IL-7 gene transduction did not alter expression of the IL-7 receptor. IL-7 transduction significantly altered tumor cell expression of intracellular adhesion molecule 1, major histocompatibility complex 1, lymphocyte function-related antigen 3, very late activation antigen beta 1, and p185neu. Peripheral blood lymphocytes cocultured with either IL-7-transduced tumor cells or tumor supernatants had enhanced cytolytic and proliferative capacities compared with coculture with control vector-transduced or parental cells. Our findings indicate that IL-7 gene transfer in NSCLC significantly augments cocultured effector activities in vitro, inhibits tumor cell proliferation, and modifies tumor cell surface phenotype. These findings suggest that IL-7 gene therapy may be effective in modifying host antitumor responses in NSCLC.

Antibodies, Monoclonal↗