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Biomedical subjects

Z Hu

Publications and source records attributed to Z Hu.

At least 325 records · Page 18Linked to original sources
PubMed1994

Modulation of benzo[a]pyrene bioactivation by glucuronidation in lymphocytes and hepatic microsomes from rats with a hereditary deficiency in bilirubin UDP-glucuronosyltransferase.

UDP-glucuronosyltransferases (UGTs) play a major role in the elimination of nucleophilic metabolites of xenobiotics, such the phenols and quinols of polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BP). In this way, UGTs may prevent the further oxidation of such metabolites to toxic reactive intermediates, which may react with lipids, DNA, RNA, and protein, thereby initiating such toxicities as cellular necrosis, birth defects, and cancer. We have shown previously in vivo and in hepatic microsomes that rats with a hereditary deficiency in bilirubin UGT (Gunn and RHA strains) have decreased glucuronidation of BP metabolites and enhanced BP covalent binding to hepatic DNA and microsomal protein, and enhanced BP embryotoxicity. We further hypothesized that a similar deficiency in BP glucuronidation, with increased BP bioactivation and covalent binding, might be observed in peripheral blood lymphocytes from UGT-deficient rats, which, if true, would suggest the utility of an analogous human lymphocyte model for evaluating the toxicological relevance of human UGT deficiencies. Such an in vitro approach is essential for human studies of environmental chemicals and drugs with a high toxicologic potential. In the current study, [7,10(-14)C]BP was preincubated with NADPH and hepatic microsomes from Wistar rats induced with beta-naphthoflavone. The supernatant from this preincubation, which contained BP reactive intermediates and hydroxylated BP metabolites, was further incubated with uridine diphosphate glucuronic acid and peripheral lymphocytes from heterozygous (j/+) and homozygous (j/j) RHA rats, which are genetically deficient in bilirubin UGT, and from congenic, homozygous (+/+) UGT-normal controls. In vivo, bilirubin glucuronidation was reduced in UGT deficiency, with progressively higher plasma concentrations of unconjugated bilirubin in j/+ and j/j UGT-deficient rats compared to +/+ UGT-normal controls (p < 0.05). In in vitro studies, glucuronide conjugates of BP were measured by high-performance liquid chromatography with a radioisotope detector, and the covalent binding of BP to microsomal protein was measured by liquid scintillation spectrometry. BP glucuronidation and covalent binding, respectively, were decreased and increased to a progressively greater degree in both hepatic microsomes and lymphocytes from j/+ and j/j UGT-deficient rats compared to +/+ UGT-normal controls (p < 0.05). Reduced BP glucuronidation in lymphocytes from UGT-deficient RHA rats correlated with elevated BP covalent binding (R2 = 0.85, p < 0.005). Both BP glucuronidation and BP covalent binding in lymphocytes significantly correlated with those reactions using hepatic microsomes from the same animals. These results in UGT-deficient lymphocytes also accurately reflected the in vivo biotransformation and covalent binding of BP in UGT-deficient rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Distribution of seven homology groups of mitochondrial plasmids in Neurospora: evidence for widespread mobility between species in nature.

A survey of mitochondrial DNAs from over 225 Neurospora and related fungal isolates from around the world uncovered three new homology groups of mitochondrial plasmids, two divergent subgroups of the Fiji plasmid family, and extended previous data about plasmid distribution patterns. Newly-discovered circular plasmids, Java and MB1, and the linear Moorea plasmids, were found in relatively-few isolates. A large proportion of isolates (51%) were found to have these or previously-discovered plasmids in the Varkud, kalilo, LaBelle, or Fiji families. Plasmids in most families were found in isolates worldwide and distributed nearly randomly with respect to species. As many as three types of plasmids were found in single isolates, and plasmids typically were found alone or in pairs in a random, independent pattern. The regional clustering of some plasmids was independent of species, providing a strong argument that horizontal transfer of plasmids occurs frequently in nature. Some plasmid families were much more diverse than others. The Fiji plasmids are a superfamily composed of distinct subgroups defined by degrees of cross-hybridization. Between some subgroups there were large regions of non-homology.

DNA, Fungal↗
PubMed1994

The intestinal uptake of "enzymatically-stable" peptide drugs in rats as influenced by D-glucose in situ.

In previous in situ and in vivo rat perfusion studies, the intestinal absorption of several low molecular weight drugs was increased by the presence of luminal D-glucose. The intent of this study was to determine the potential of this fed-state effect to improve the intestinal uptake of poorly permeable, small peptide and peptide-like drugs. Jejunal wall permeabilities (Pw*) of di-(D-kyotorphin), tri-(cephradine), hexa-(growth hormone releasing peptide, GHRP-6) and octa-(octreotide, a somatostatin analogue) peptides and corresponding net water fluxes were determined in rats using an in situ single-pass perfusion technique. Glucose was shown to enhance the uptake of the smaller (di- and tri-) peptides but not the larger peptides despite the fact that glucose elicited a significant net water absorption with each of the four peptide drugs. It is concluded that glucose enhances jejunal permeabilities of smaller peptides by solvent drag and the enhancement is limited in situ by peptide molecular size. The studies with nonmetabolizable 3-O-methylglucose suggest that the augmentation of the proton gradient across the transmucosal membrane by glucose contributes to the carrier-mediated transport observed with the smaller peptides.

3-O-Methylglucose↗
PubMed1994

Repeated polyketide synthase modules involved in the biosynthesis of a heptaene macrolide by Streptomyces sp. FR-008.

Genes for biosynthesis of a Streptomyces sp. FR-008 heptaene macrolide antibiotic with antifungal and mosquito larvicidal activity were cloned in Escherichia coli using heterologous DNA probes. The cloned genes were implicated in heptaene biosynthesis by gene replacement. The FR-008 antibiotic contains a 38-membered, polyketide-derived macrolide ring. Southern hybridization using probes encoding domains of the type I modular erythromycin polyketide synthase (PKS) showed that the Streptomyces sp. FR-008 PKS gene cluster contains repeated sequences spanning c. 105kb of contiguous DNA; assuming c. 5 kb for each PKS module, this is in striking agreement with the expectation for the 21-step condensation process required for synthesis of the FR-008 carbon chain. The methods developed for transformation and gene replacement in Streptomyces sp. FR-008 make it possible to genetically manipulate polyene macrolide production, and may later lead to the biosynthesis of novel polyene macrolides.

Anti-Bacterial Agents↗
PubMed1994

Liposomes: a novel topical delivery system for pharmaceutical and cosmetic applications.

This review will highlight work done in our laboratories evaluating topical liposomal delivery in a wide variety of animal models and human skin using both in vivo and in vitro techniques. The mechanism by which liposomes facilitate deposition of drugs into the skin and some potential applications of topically applied liposomes will be discussed. Particular emphasis will be placed on the development of analytical techniques that allow the quantification of drug levels in the various skin strata and in pilosebaceous structures. Appropriate models of skin representing the two cases, as well as those wherein both routes are available for skin deposition, were examined using a wide variety of liposomal preparations containing radiolabeled and fluorescent molecules as marker compounds.

Animals↗
PubMed1994

Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat.

BACKGROUND: Stem cell factor (SCF) and its receptor, c-kit, are known to play important roles in hematopoiesis, melanogenesis, and gametogenesis. The biologic effects of the SCF/c-kit system are believed to involve survival, proliferation, and migration of early stem cell progeny. Although SCF and c-kit receptor are widely expressed during normal embryonic development, their expression in the adult is limited. EXPERIMENTAL DESIGN: The expression of SCF and c-kit genes was examined during liver regeneration via the oval cell compartment utilizing partial hepatectomy (PH) combined with the administration of a noncarcinogenic dose of 2-acetylaminofluorene (AAF) for 8 days (AAF/PH model). RESULTS: Both the ligand and the receptor genes were expressed during the early stages of oval cell proliferation after partial hepatectomy in the AAF/PH model, while neither simple partial hepatectomy nor AAF administration alone induced a noticeable expression of the SCF/c-kit system. The level of SCF mRNA increased within 12 hours after partial hepatectomy and reached a peak around day 4. Thus, the expression of SCF preceded the major expansion of the oval cell compartment. The level of c-kit transcripts gradually increased from the 12-hour time point and stayed elevated until day 11, when a large proportion of the oval cells differentiated into small basophilic hepatocytes. Separation of liver cells at day 3 in the AAF/PH model into parenchymal and nonparenchymal fractions demonstrated that the expression of both SCF and c-kit receptor genes was restricted to the nonparenchymal cells. Furthermore, in situ hybridization revealed that the c-kit transcripts were restricted to oval cells, whereas the SCF transcripts were expressed in both oval cells and Ito cells. CONCLUSIONS: The transcripts for the c-kit receptor are expressed in the early progeny of the hepatic stem cells. The SCF/c-kit system may, possibly in combination with other growth factor/receptor systems, be involved in the early activation of the hepatic stem cells as well as in the expansion and differentiation of oval cells.

Animals↗
PubMed1994

Hepatic regeneration in vitamin A-deficient rats: changes in the expression of transforming growth factor alpha/epidermal growth factor receptor and retinoic acid receptors alpha and beta.

We have studied the effect of vitamin A deficiency on the expression of transforming growth factor alpha (TGF-alpha), hepatocyte growth factor, acidic fibroblast growth factor, and TGF-beta 1 after partial hepatectomy of vitamin A-supplemented and vitamin A-deficient rats. In addition, the expressions of epidermal growth factor receptor and retinoic acid receptors alpha (RAR alpha) and beta (RAR beta) were studied. Partial hepatectomy was performed on the animals from the vitamin A-supplemented and -deficient groups at the age of 10 weeks when the weights of the animals on the deficient diet had reached a plateau. Two animals from each group were sacrificed before the operation and also 12, 24, 48, and 72 h and 5 days after the operation. Partial hepatectomy of the vitamin A-deficient rats leads to a focal necrosis of liver followed by a rapid restoration of liver mass. Expression of the TGF-alpha and epidermal growth factor receptor was highly elevated in the livers of deficient animals after partial hepatectomy. In the vitamin A-supplemented animals, the level of epidermal growth factor receptor was down-regulated following partial hepatectomy. Proliferation of oval cells in vitamin A-deficient livers following partial hepatectomy and subsequent increase in 2.1-kilobase alpha-fetoprotein mRNA was observed, suggesting an activation of the stem cell compartment. Another unexpected result was an inverse relationship between RAR beta and RAR alpha expression, the latter becoming the major species after partial hepatectomy in animals on the vitamin A-deficient regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Argon laser photocoagulation in the treatment of central serous chorioretinopathy].

Thirty-six cases (41 eyes) with central serous chorioretinopathy were treated by using argon laser photocoagulation. The results showed that the number of eyes with vision equal to or more than 1.0 increased from 7 (17.1%) pre-laser to 26 (63.4%) post-laser, while the number of eyes with vision less than 1.0 decreased from 25 (61%) pre-laser to 6 (14.6%) post-laser. The subretinal fluid was almost entirely absorbed from 1 week to 1 month after, and central fovea reflex could be seen in some cases. The results indicate that the vision prognosis is strongly related to the duration of the disease, but the direction of leakage to the fovea, the distance between the leakage and the fovea, and the dimension of sensory retina detachment are factors which weakly affect the post-laser vision.

Adult↗
PubMed1994

Congenital perforation of the triangular fibrocartilage of the wrist.

The triangular fibrocartilages (TFC) of 136 wrist joints from 48 fetuses and 20 infants fresh cadavers without any evidence of known deformity and injury were studied. Perforations of the TFC were found not only in infants (18.8%), but also in fetuses (25%). The difference between the incidences of the perforations in the two groups is not statistically significant (P > 0.05). Furthermore, we did not find that perforation of the TFC is correlated with either sex or side of wrists (P > 0.05). Histologically, the vascularity and cellularity of the TFC have no significant correlation with the absence or presence of perforation in it. We believe that, besides trauma, inflammation and degeneration, some perforations of the TFCs are congenital in origin, which all take the form of fissure and are located mainly in the radial half of the TFC.

Cartilage, Articular↗
PubMed1994

[Observation on prevention of hepatitis B virus transmission from mother to baby by hepatitis B vaccine].

Forty-two new-born infants whose mothers had been given HBV vaccine before marriage were undergone medical examination for six years. The results showed that the six-month seroconversion rates of anti-HBs among those infants, whose mothers had been immunized successfully, were 90.00% (9/10), and no one was infected by HBV. But the rates of those infants whose mothers were found to be HBsAg(+) and HBsAg/HBeAg(+) before or after marriage were 20.00% (2/10) and 18.18% (4/22), respectively, being much lower than the former. The rates of HBsAg(+) were 70.00% (7/10) and 68.18% (15/22), respectively. This led to the conclusion that immunization with HBV vaccine before marriage will partly break the HBV transmission chain of "couples-mother and her baby-population".

Adult↗
PubMed1994

Bulk isolation and identification of fish genes by cDNA clone tagging.

The fish has long been a popular research model for various disciplines in the life sciences, but its molecular biology remains largely unexplored, and the number of fish genes identified at present is still limited. To increase the repertoire of fish genes to facilitate further research, we have embarked on cDNA clone tagging studies in several teleosts. The basic procedure is partial sequencing of randomly selected cDNA clones by a single sequencing reaction to obtain nucleotide sequences of about 200 to 300 bp for each clone. These partial DNA sequences can be used as tags to identify fish homologous genes by searching for sequence similarity in DNA databases. By this method, we have sequenced a total of 265 clones from pituitary and liver cDNA libraries from five species of fish and identified 83 clones encoding 55 different genes. These 55 genes are described for the first time in their species, and 37 of them are described for the first time in fish. These preliminary data indicate that cDNA clone tagging is useful for rapidly increasing the number and availability of genes in teleosts. Several applications of these tagged random clones are discussed.

Animals↗
PubMed1993

Purification, complete amino acid sequence and structural characterization of the heat-stable sweet protein, mabinlin II.

A new sweet protein, named mabinlin II, was extracted with 0.5 M NaCl solution from the seeds of Capparis masaikai Lévl. and purified by ammonium sulfate fractionation, carboxymethylcellulose-Sepharose ion-exchange chromatography and gel filtration. The sweetness of mabinlin II was unchanged by at least 48 h incubation at nearly boiling temperature. Purified mabinlin II thus obtained gave a single band having a molecular mass of 14 kDa on SDS/PAGE. In the presence of dithiothreitol, mabinlin II gave two bands having molecular masses of 4.6 kDa and 5.2 kDa on SDS/PAGE. Two peptides (A chain and B chain) were separated from reduced and S-carboxamidomethylated mabinlin II by HPLC. The amino acid sequences of the A chain and B chain were determined by the automatic Edman-degradation method. The A chain and B chain consist of 33-amino-acid and 72-amino-acid residues, respectively. The A chain is mostly composed of hydrophilic amino acid residues and the B chain also contains many hydrophilic residues. High similarity was found between the amino acid sequences of mabinlin II and 2S seed storage proteins, especially 2S albumin AT2S3 in Arabidopsis thaliana (mouse-ear cress).

Amino Acid Sequence↗
PubMed1993

Physical mapping of buzura suppressaria nuclear polyhedrosis virus genome.

A physical map of the genome of buzura suppressaria singly-enveloped nuclear polyhedrosis virus (BsSNPV) was determined using six restriction endonucleases (RE), singly or in pairs, and Southern hybridizations of cloned or gel-purified DNA fragments. The maps of the genomes of BsSNPV and autographa californica multiply-enveloped nuclear polyhedrosis virus (AcMNPV) were different.

Animals↗
PubMed1993

Ontogeny of GH mRNA and GH secretion in male and female rats: regulation by GH-releasing hormone.

Growth hormone-releasing hormone (GHRH) has been shown in vitro to increase proliferation of pituitary somatotrophs, to increase transcription of the GH gene, to promote accumulation of GH mRNA, and to stimulate GH release. The in vivo involvement of hypothalamic GHRH in regulating GH mRNA content had never been clearly documented. We studied pituitary GH mRNA and GH contents and serum concentrations of GH and insulin-like growth factor I (IGF-I) in rats of both sexes during pubertal growth spurt and investigated the effects of GHRH deficiency (brought about by neonatal administration of monosodium glutamate, MSG) and exogenous GHRH administration on these parameters. In both sexes, GH mRNA content increased three- to fourfold between 4 and 12 wk of life and declined thereafter toward 33 wk of life. This was accompanied by virtually parallel changes in pituitary GH content and in serum IGF-I. Neonatal MSG abolished the pubertal increases in GH mRNA, pituitary GH, and serum IGF-I and severely impaired growth rate. Exogenous GHRH (25 micrograms/kg sc every 8 h for 7 days) given to intact animals between 6 and 7 wk of life significantly augmented pituitary GH mRNA content but was less effective in MSG-treated rats. We conclude that 1) pubertal growth spurt in both sexes is associated with rising pituitary GH mRNA content; 2) GHRH deficiency abolishes the puberty-associated increase in GH synthesis and secretion and attenuates somatic growth rate; and 3) exogenous GHRH augments GH mRNA content. Thus puberty-associated augmentation of GHRH secretion is an important mechanism of somatic growth.

Aging↗