Biomedical subjects

Z Gu

Publications and source records attributed to Z Gu.

At least 181 records · Page 10Linked to original sources

PubMed1994

Generation of multiple drug resistance by sequential in vitro passage of the human immunodeficiency virus type 1.

We have sequentially passaged both laboratory and clinical isolates of the human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of increasing concentrations of different drugs to derive viral variants that are multiply resistant to various combinations of ddC, ddI, d4T and AZT. The EC50 values obtained for the viruses thus generated varied between 50-100 times above those of parental wild-type strains in the case of AZT, 20-30 times for d4T, but only 10-15 times for ddI and ddC. Cultivation of AZT-resistant viruses in the presence of increasing concentrations of ddI yielded viruses that were resistant to the latter compound, with no apparent decrease in susceptibility to AZT. Sometimes, viruses selected for resistance against ddI were cross-resistant as well against ddC, although most viruses selected for resistance to ddC were not cross-resistant to ddI. Combinations of two or three of these compounds inhibited replication of HIV variants that displayed resistance to the same drugs when tested individually. No emergence of drug resistance was demonstrable when combinations of drugs were employed simultaneously in these selection protocols or when single drugs were used in concert with interferon-2 alpha or high dilutions of virus-neutralizing antisera. Cloning and sequencing of some viruses resistant to each of AZT, ddI, and ddC revealed the simultaneous presence of mutations at sites 41, 74, 184 and 215 within the HIV pol gene open reading frame.

Antiviral Agents↗

PubMed1994

BMS-180560, an insurmountable inhibitor of angiotensin II-stimulated responses: comparison with losartan and EXP3174.

1. This study compares the activity of BMS-180560 (2-butyl-1-chloro-1-[[1-[2-(2H-tetrazol-5-yl)phenyl]-1H-indol-4- yl]methyl]-1H-imidazole-5-carboxylic acid), an insurmountable angiotensin II (AII) receptor antagonist, with that of losartan and EXP3174 in functional and biochemical models of AII-receptor activation. 2. BMS-180560 selectively inhibited [125I]-Sar1Ile8AII ([125I]SI-AII) binding to rat aortic smooth muscle (RASM) cell and rat adrenal cortical AT1 receptors (Ki = 7.6 +/- 1.2 and 18.4 +/- 3.9 nM respectively) compared to adrenal cortical AT2 receptors (Ki = 37.6 +/- 1.3 microM). The Ki values of BMS-180560 and EXP3174, but not losartan, varied as a function of the BSA concentration used in the assays, indicating that the diacid drugs bound to albumin. 3. BMS-180560 (3-300 nM) increased the KD of SI-AII for RASM cell AT1 receptors. Only at high concentrations of BMS-180560 (300 nM) were Bmax values decreased. 4. BMS-180560 inhibited AII-stimulated contraction of rabbit aorta with a calculated KB = 0.068 +/- 0.048 nM and decreased maximal AII-stimulated contraction at 1 nM BMS-180560 by 75%. In the presence of 0.1% BSA, a higher KB value (5.2 +/- 0.92 nM) was obtained. Losartan behaved as a competitive antagonist with a KB = 2.6 +/- 0.13 nM. Contraction stimulated by endothelin-1, noradrenaline, KCl, or the TXA2 receptor agonist U-46619 were unaffected by BMS-180560 (1 nM). 5. AII stimulated the acidification rates of RASM cells as measured by a Cytosensor microphysiometer with an EC50 of 18 nM. Losartan (30 nM) shifted the AII concentration-effect curves in a competitive manner whereas BMS-180560 (0.01 and 0.1 nM) decreased the maximum responses by 60 and 75% respectively. Inhibition by losartan and BMS-180560 could be reversed following washout although recovery took longer for BMS-180560. 6. In [3H]-myoinositol-labelled RASM cells, losartan (30 and 200 nM), shifted the EC50 for AII-stimulated [3H]-inositol monophosphaste formation to higher values, with no change in the maximal response. By contrast, EXP3174 (0.1 to 1 nM) decreased the maximal response in a concentration-dependent manner (17-55%). BMS-180560 (3 and 10 nM) increased the EC50 for AII and decreased the maximum response by 30 and 80% respectively. The inhibition by EXP3174 and BMS-180560 could be reversed by inclusion of losartan (200 nM) indicating that the inhibition was not irreversible. 7. In conclusion, BMS-180560 is a potent, specific, predominantly competitive, reversible All receptor antagonist, which displays insurmountable receptor antagonism. At concentrations of BMS-180560 which have no effect on receptor number, BMS-180560 produced insurmountable antagonism of AII-stimulated second messenger formation, extracellular acidification, and smooth muscle contraction.

Adrenal Cortex↗

PubMed1994

Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.

The technique of in vitro selection was used to generate variants of the human immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC). Most of the pol regions of such viruses, including the complete reverse transcriptase open reading frame and portions of flanking protease and integrase genes, were cloned and sequenced, using PCR-based procedures. Mutations were variously detected at amino acid site 65 (Lys-->Arg; AAA-->AGA) and at a previously reported codon, site 184 (Met-->Val; ATG-->GTG). We introduced the site 65 mutation into the pol gene of infectious, cloned HxB2-D DNA by site-directed mutagenesis in order to confirm by viral replication assay the importance of this site in conferring resistance to ddC. The recombinant virus possessed greater than 10-fold resistance against this compound in comparison with parental HxB2-D. Cross-resistance of approximately 20- and 3-fold, respectively, was detectable against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine and 2',3'-dideoxyinosine but not against 3'-azido-3'-deoxythymidine. Combinations of the site 65 and 184 mutations did not yield levels of resistance higher than those attained with the site 65 mutation alone. The presence of the site 65 mutation was confirmed by PCR analysis of peripheral blood mononuclear cells from patients on long-term ddC therapy in 4 of 11 cases tested. Viruses that possessed a ddC resistance phenotype were isolated from subjects whose viruses contained the site 65 mutation in each of four instances. Four of these clinical samples were also demonstrated to possess the Met-184-->Val mutation, and one of them possessed both the Lys-65-->Arg and Met-184-->Val substitutions. Direct cloning and sequencing revealed the site 65 mutation in viruses isolated from these individuals.

Amino Acid Sequence↗

PubMed1994

Properties of a pentapeptide inhibitor of peptidyltransferase that is essential for cat gene regulation by translation attenuation.

Inducible chloramphenicol resistance genes cat and cmlA are regulated by translation attenuation. For both genes, the leader codons that must be translated to deliver a ribosome to the induction site specify a peptide that inhibits peptidyltransferase in vitro. The antipeptidyltransferase activity of the peptides is thought to select the site of ribosome stalling that is essential for induction. Using variations of the cat-86 leader-encoded 5-mer peptide MVKTD, we demonstrate a correlation between the in vitro antipeptidyltransferase activity and the ability of the same peptide to support induction by chloramphenicol in vivo. MVKTD footprints to nucleotides 2058, 2059, and 2060 in 23S rRNA. In vivo methylation of nucleotide 2058 by the ermC methylase interferes neither with cat-86 induction nor with peptide inhibition of peptidyltransferase. The methylation eliminates the competition that normally occurs in vitro between erythromycin and MVKTD. MVKTD inhibits the peptidyltransferase of several eubacteria, a representative Archaea species, and the eukaryote Saccharomyces cerevisiae. Bacillus stearothermophilus supports the in vivo induction of cat-86, and the RNA that is phenol extracted from the 50S ribosomes of this gram-positive thermophile is catalytically active in the peptidyltransferase assay and sensitive to peptide inhibition. Our results indicate that peptidyltransferase inhibition by a cat leader peptide is essential to induction, and this activity can be altered by minor changes in the amino acid sequence of the peptide. The broad range of organisms shown to possess peptide-inhibitable peptidyltransferase suggests that the target is a highly conserved component of the ribosome and includes 23S rRNA.

Amino Acid Sequence↗

PubMed1994

Comparison of cord blood and peripheral blood mononuclear cells as targets for viral isolation and drug sensitivity studies involving human immunodeficiency virus type 1.

We have shown that umbilical cord blood mononuclear cells (CBMC) are at least as sensitive as peripheral blood mononuclear cells (PBMC) for isolation of human immunodeficiency virus type 1 from the PBMC of infected individuals. Viral replication was more efficiently monitored by a p24 antigen capture assay than by a viral reverse transcriptase test, regardless of whether CBMC or PBMC were employed. We also found that CBMC and PBMC yielded similar results with regard to the susceptibility profiles of both wild-type and drug-resistant variants of human immunodeficiency virus type 1 for 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine. Finally, viruses isolated on CBMC could be routinely grown on PBMC and vice versa.

Antiviral Agents↗

PubMed1994

Effects of alterations of primer-binding site sequences on human immunodeficiency virus type 1 replication.

The human immunodeficiency virus type 1 genomic RNA primer-binding site (PBS) sequence comprises 18 nucleotides which are complementary to those at the 3' end of the replication initiation primer tRNA(3Lys). To investigate the role of the PBS in viral replication, we either deleted the original wild-type PBS (complementary to tRNA(3Lys) or replaced it with DNA sequences complementary to either tRNA(1,2Lys) or tRNA(Phe). Transfection of COS cells with such molecular constructs yielded similar levels of viral progeny that were indistinguishable with regard to viral proteins and tRNA content. Virus particles derived from PBS-deleted molecular clones were noninfectious for MT-4, Jurkat, and CEM-T4 cells. However, infectious viruses were derived from constructs in which the PBS had been altered to sequences complementary to either tRNA(1,2Lys) or tRNA(Phe), although mutated forms showed significant lags in replication efficiency in comparison with wild types. Molecular analysis of reverse-transcribed DNA in cells infected by the mutated viruses indicated that both tRNA(1,2Lys) and tRNA(Phe) could function as primers for reverse transcription during the early stages of infection. Sequencing of full-length proviral DNA, obtained 6 days after infection, revealed the mutated PBS, indicating that a complete cycle of reverse transcription had occurred. During subsequent rounds of infection, reversion of the mutated PBS to wild-type sequences was observed, accompanied by increased production of viral gene products. Reversion to wild-type PBS sequences was confirmed both by specific PCR analysis, using distinct primer pairs, and by direct sequencing of amplified segments. We also performed endogenous in vitro reverse transcription experiments in which synthesis of minus-strand strong-stop viral DNA was primed from a synthetic RNA template containing a PBS complementary to various tRNA isoacceptors. These results showed that tRNA(3Lys) was a much more efficient primer of such reactions than either tRNA(1,2Lys) or tRNA(Phe).

Animals↗

PubMed1994

Identification of novel mutations that confer drug resistance in the human immunodeficiency virus polymerase gene.

We generated variants of the human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) by in vitro selection in MT-4 cells. Portions of flanking protease and integrase sequences as well as the complete reverse transcriptase (RT) open-reading frame of these viruses were cloned and sequenced, using polymerase chain reaction (PCR)-based methods. Mutations were observed at amino acid position 65 (Lys-->Arg; AAA-->AGA) when ddC was employed in the selection procedure and at site 50 (Ile-->Thr; ATT-->ACT) when d4T was used. We confirmed the ability of these mutations to confer diminished sensitivity for these compounds by site-directed mutagenesis, in which these mutations were inserted into the pol gene of infectious recombinant HXB2-D DNA. Viruses that contained the site 65 mutation possessed approximately 5-10 fold resistance against ddC when compared with wild-type HXB2-D. The site 50 mutation conferred approximately 30-fold resistance to d4T in these same assays. Similar results were obtained using primary cord blood lymphocytes in drug resistance assays, indicating that these mutations could confer drug resistance in more than one cell type and that the respective mutations could be expressed in cells of primary origin. No cross-resistance against 3'-azido-3'-deoxythymidine (AZT) was noted for either the site 65 or 50 mutations.

Drug Resistance↗

PubMed1994

DNA damage induced p53 mediated transcription is inhibited by human papillomavirus type 18 E6.

Cervical cancer is similar to other human cancers in that it develops through a multistep process. However, infection with oncogenic human papillomaviruses (HPVs) is believed to be essential for the initiation of this disease. Although HPV may play a central role in the early stages of neoplasia, the accumulation of mutations in an assortment of genes precedes the development of malignant cervical carcinoma. The mechanisms by which abnormalities accumulate are various, but it is possible that viral proteins are involved. In particular, the viral E6 oncoprotein has been shown to interact with the cellular tumour suppressor protein p53, which is involved in DNA damage repair pathways. Hence, E6 may contribute to the genomic instability through this interaction with p53. We have tested this hypothesis by monitoring the effects of E6 upon DNA damage induced p53 transcriptional activity. This study shows that HPV-18 E6 inhibits p53 transcriptional activity following genotoxic stress with UV radiation. No effect was observed when a mutant E6 unable to direct the degradation of p53 was included in this assay. These results suggest that continued E6 expression may contribute to the accumulation of DNA damage associated with the progression of cervical cancer.

Amino Acid Sequence↗

PubMed1993

Expression, purification, and RNA-binding properties of HIV-1 p15gag nucleocapsid protein.

We have cloned and expressed HIV-1 gag p15 nucleocapsid protein (NCp15) in the form of a 41-kDa fusion polypeptide with glutathione-S-transferase (GST-NCp). The recombinant protein was rapidly degraded in bacterial lysates unless Zn2+ and Cd2+ were present in the extraction buffer. Inclusion of these metals stabilized the protein, allowing facile purification of GST-NCp by affinity chromatography. The native NCp15 was readily prepared from GST-NCp by proteolytic cleavage with thrombin. Both GST-NCp and the processed NCp15 were able to bind RNA containing sequences from the 5'-end of the HIV-1 genome. This binding was unaffected by the absence or the presence of Zn2+; however, the binding of RNA was absolutely dependent on the presence of K+. The GST-NCp fusion protein was nonselective in the binding of RNA, with all transcripts, including antisense and non-HIV RNA, binding with equal efficiency. In contrast, NCp15 was highly selective in binding of RNA. Sequences within nucleotides 1244-1412 of the HIV-1 proviral genome were found necessary for maximal binding of RNA to NCp15.

Base Sequence↗

PubMed1993

Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.

Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder associated with multisystem clinical disease. We analyzed PCR amplified products from patients' RNA and genomic DNA. Direct sequencing of the entire coding region of the CBS gene revealed a G-919 to A transition in exon 8, resulting in replacement of Gly 307 by Ser (G307S) in the protein. The mutation was detected in one allele of patient L171 of French/Scottish ancestry and in both alleles of patient L198 of Irish ancestry. Amplifying and sequencing exon 8 from the genomic DNA showed that both parents of L198 were heterozygotes for G307S. The pathogenicity of the mutation was demonstrated in an expression experiment. The mutant protein was apparently stable in E.coli extracts and lacked catalytic activity. Sequencing of exon 8 revealed the G307S mutation in five additional families. All patients have pyridoxine nonresponsive homocystinuria. We have now observed this mutation in 9 of 52 apparently unrelated alleles of varied ethnic backgrounds. All 9 are from patients with Celtic (Irish/English/Scottish/French) ancestry in either one or both parents. The G307S mutation was detected in 50% (9 of 18) of the Celtic alleles in our series. The second mutation found in exon 8 is the I278T mutation, which was described previously in one allele of a pyridoxine responsive patient. This missense mutation was detected in one allele of a pyridoxine nonresponsive patient and in both alleles of a pyridoxine responsive patient. The latter suggests that I278T is probably associated with pyridoxine responsiveness.

Adult↗

PubMed1993

Parallel induction strategies for cat-86: separating chloramphenicol induction from protein synthesis inhibition.

Induction of cat-86 translation results from the stalling of a ribosome at a discrete location in the leader region of the transcript. Stalling destabilizes an adjacent region of secondary structure that sequesters the cat-86 ribosome binding site, thereby activating cat-86 translation. Two well characterized antibiotics, chloramphenicol and erythromycin, induce cat-86 by stalling a ribosome at the appropriate leader site. Here we demonstrate differences between the two antibiotics with respect to induction. First, induction by chloramphenicol is dependent on nucleotides in the leader sequence that are different from those necessary for erythromycin induction. Second, variants of Bacillus subtilis that are chloramphenicol resistant because of chromosome mutations permit cat-86 induction by chloramphenicol, whereas erythromycin-resistance host mutations block or greatly reduce cat-86 induction by erythromycin. Third, selected strains of B. subtilis bearing alterations in proteins of the 50S ribosomal subunit interfere with cat-86 induction by chloramphenicol, yet these strains are chloramphenicol sensitive. Lastly, induction by chloramphenicol is not reversed by removal of the antibiotic whereas erythromycin induction is reversible. The data indicate that chloramphenicol induction results from an effect of the drug that is not identical to its role as a general inhibitor of ribosome elongation. Induction by erythromycin, on the other hand, could not be distinguished from its antibiotic activity.

Bacillus subtilis↗

PubMed1993

Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.

We selected in vitro human immunodeficiency virus type 1 variants that are resistant to each of 2',3'-dideoxycytidine (ddC) and the racemic mixture of 2',3'-dideoxy-3'-thiacytidine (BCH-189). The median effective concentrations of ddC and BCH-189 obtained for the resistant viruses ranged between 10 and 50 times above those for parental wild-type strains, and extensive cross-resistance was observed against 2',3'-dideoxyinosine (ddI) but not 3'-azido-3'-deoxythymidine (AZT). Two dimer compounds, in which either AZT and ddI or AZT and BCH-189 were linked through phosphodiester linkages, did not permit the emergence of variants resistant to BCH-189, ddI, or AZT but were ineffective at inhibiting the replication of AZT-resistant viruses.

Acquired Immunodeficiency Syndrome↗

PubMed1993

The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.

Variants of human immunodeficiency virus type 1 that display 500- to 1,000-fold resistance to the (-) enantiomer of 2'-deoxy-3'-thiacytidine and approximately 4- to 8-fold resistance to 2',3'-dideoxycytidine and 2',3'-dideoxyinosine have been generated through in vitro selection with the former compound. The polymerase regions of several of these resistant viruses shared a codon alteration at site 184 (ATG-->GTG; methionine-->valine), a mutation previously associated with low-level resistance to 2',3'-dideoxycytidine. The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1.

Antiviral Agents↗

PubMed1993

Peptidyl transferase inhibition by the nascent leader peptide of an inducible cat gene.

The site of ribosome stalling in the leader of cat transcripts is critical to induction of downstream translation. Site-specific stalling requires translation of the first five leader codons and the presence of chloramphenicol, a sequence-independent inhibitor of ribosome elongation. We demonstrate in this report that a synthetic peptide (the 5-mer) corresponding to the N-terminal five codons of the cat-86 leader inhibits peptidyl transferase in vitro. The N-terminal 2-, 3-, and 4-mers and the reverse 5-mer (reverse amino acid sequence of the 5-mer) are virtually without effect on peptidyl transferase. A missense mutation in the cat-86 leader that abolishes induction in vivo corresponds to an amino acid replacement in the 5-mer that completely relieves peptidyl transferase inhibition. In contrast, a missense mutation that does not interfere with in vivo induction corresponds to an amino acid replacement in the 5-mer that does not significantly alter peptidyl transferase inhibition. Our results suggest that peptidyl transferase inhibition by the nascent cat-86 5-mer peptide may be the primary determinant of the site of ribosome stalling in the leader. A model based on this concept can explain the site specificity of ribosome stalling as well as the response of induction to very low levels of the antibiotic inducer.

Amino Acid Sequence↗

PubMed1993

Clinical correlates and molecular basis of HIV drug resistance.

It has been widely reported that zidovudine (ZDV)-resistant variants of human immunodeficiency virus type 1 (HIV-1) can be isolated from patients undergoing prolonged therapy with this drug. At the same time, treatment of HIV-infected individuals with ZDV and other forms of nucleotide therapy, including didanosine (ddI), have enabled patients to live longer than would otherwise be the case and to enjoy improved quality of life. HIV resistance to ZDV, ddI, and other nucleosides is attributable to a series of point mutations within the pol gene of HIV-1 that encodes the viral enzyme, reverse transcriptase (RT). This is not surprising as the virus is known to replicate at high rates in infected individuals; moreover the RT that mediates transcription of proviral DNA from viral genomic RNA is known to be highly error prone. Thus, mutants of HIV-1, which possess a drug-resistance phenotype and genotype, may be expected to emerge under the selective pressure of long-term antiviral chemotherapy. This article describes a novel mutation at site 184 within the pol gene that accounts for resistance against both ddI and zalcitibine (ddC). HIV drug resistance occurs most commonly in individuals with low CD4 cell counts who have progressed to more serious forms of disease. Moreover, viruses obtained from patients with AIDS generally display higher levels of resistance, relative to pretreatment isolates, than do viruses from patients with more-limited illness. Although observations of drug resistance can be correlated with disease progression and a weakened immune system, it is still unclear whether a cause-and-effect relationship exists. Because of the error-prone nature of viral RT and the fact that the HIV-1 genome can mutate efficiently, it can be anticipated that viral drug resistance may emerge for all forms of nucleotide therapy to be offered in the future. In addition, resistance may also become apparent with regard to drugs that block HIV replication by acting at sites within the viral replication cycle other than RT.

CD4-Positive T-Lymphocytes↗

PubMed1993

[Emancipation of the developmental block of early rat embryos by protein factors excreted from rabbit oviduct epithelial cells in culture].

Experiments were designed to evaluate the ability of rabbit oviduct epithelial cells (ROEC) or ROEC conditioned medium to promote the development of rat eggs fertilized in Vivo or in Vitro. 61.73% of the eggs fertilized in Vitro and 73.33% of the eggs fertilized in Vivo cocultured with ROEC overcame the 2-cell block (Plate I, tables 1 and 2). Similarly, 67.99% of the eggs fertilized in Vitro cultured in ROEC conditioned medium developed over the 2-cell stage, and nearly half of them developed to morula and blastocysts stage (Table 3). By using 35S-methionine incorporation and autoradiography methods, several polypeptides, with molecular weight of 135 Kd, 68 Kd, 55 Kd, 51 Kd and 44 Kd respectively (Fig. 1), were excreted from rabbit oviduct epithelial cells and found in the ROEC conditioned medium. The possibility of entrance of the ROEC proteins into the developing embryo was tested by determining whether any of the secreted proteins bound to the zona pellucida. The results of iodination by using 125I-containing acylating agent labelling method showed that the 68 Kd and 55 Kd proteins were bound onto the zona pellucida of rat eggs co-cultured with ROEC in vitro for 24 h (Fig. 2). Studies concerning the problem that whether these two secreted proteins are the key factors to promote the development of early embryos and the transition of maternal to zygotic control of embryo development are undertaking.

Animals↗

PubMed1993

[Experimental analysis of mechanism concerning the environmental temperature effect on acquisition of capability in toad oocyte to resume meiotic division].

Full-grown oocytes derived from Bufo bufo gargarizans rearing in high temperature environment (28-30 degrees C), called high temperature oocytes, never underwent germinal vesicle breakdown (GVBD) after progesterone stimulation, no MPF was detected in their ooplasm, but some events which manifested normally at the beginning of progesterone induced maturation process were revealed in these oocytes. It is worth notice an another kind of maturation promoting substance(s) appeared in the ooplasm of high temperature oocyte after the hormone treatment, which was capable of triggering the resumption of meiotic division of the full-grown oocytes derived from hibernating toad (called low temperature oocytes). It is a hibernation factor-dependent maturation promoting substance (HF-MPS), which appeared after decrease of the oocyte endogenous cAMP level. Its appearance depended upon the oocyte protein synthesis, and its activity to inducing GVBD of low temperature oocytes did not inhibited by puromycin. HF-MPS differs from MPF in maturation promoting activity, as low temperature (10 degrees C) delayed obviously HF-MPS' activity but did not influence the rate of GVBD induced by MPF. Further more, probably due to the lack of "hibernation factor(s)", no expression of p34cdc2 gene was detected in high temperature oocytes (unpublished data), neither HF-MPS nor MPF could amplify autocatalytically in the oocytes. So the low temperature (below 15 degrees C) was found to be indispensable for the toad oocyte maturation. If one day we can prove HF-MPS appeared also in the course of oocyte maturation induced by progesterone, the relationship between HF-MPS and MPF may be: [formula: see text] All these discoveries indicated above make a reasonable explanation of the geographical distribution of the toad which was restricted in the region north to the 23 degrees north latitude and east to the 100 degrees east longitude in China.

Animals↗

PubMed1993

[Effects of air pollution on health of residents in vicinity of an electrometallurgical factory in Chengdu].

Air pollution in an electrometallurgical plant in Chengdu was monitored in 1988. Results showed that atmospheric TSP and Ni concentrations in the vicinity of the plant were higher than those in control area; and TSP content higher than its health standard level. A population of 262 children was physically examined in the same pollution and control areas in May, 1988. Physical examinations were as follows:otorhinolaryngological examination, skin patch test of Ni and Co, immune function test (including PHA skin test, salivary LZM content), Ni levels in human hair and urine etc. We found that body burdens of Ni in population of pollution area increased because of the pollution of Ni compounds in the atmosphere. Hair Ni content in pollution area was significantly higher than that in control area, and the positive rate of Ni skin patch test was also markedly higher than that in control area. Case history indicated that there was a significant difference in Ni content as detected by otorhinolaryngological examinations between the pollution and control areas. Some measures were suggested to improve the air quality based on the study.

Adolescent↗