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Biomedical subjects

J Shi

Publications and source records attributed to J Shi.

At least 325 records · Page 18Linked to original sources

[Multivariate analysis on prognostic factors for acute myocardial infarction during acute period noncondition stepwise logistic model].

The relationship between baseline factors defined at 4.3 +/- 1.8 hr after onset of acute myocardial infarction and 28-day survival in 319 patients admitted into the China Medical University was evaluated. The case fatality rate during acute period was 17.9%. Univariate statistics identified a significant relationship between 5 of these factors and survival. Multivariate noncondition stepwise logistic model analysis identified four factors as being most closely related to survival: (1) heart failure; (2) arrhythmia; (3) age; (4) history of essential hypertension. It is concluded that heart failure during the acute period of acute myocardial infarction is the most important baseline factor for prediction of 28-day survival.

Aged↗

Thyrotropin-releasing hormone (TRH) neurons sprout in cervical spinal cord of Wobbler mouse.

The present study was undertaken to quantify the immunocytochemical changes for thyrotropin-releasing hormone (TRH) within the ventral horn of the cervical spinal cord from Wobbler (wr/wr) mice selected at postnatal ages 3 weeks to 5 months compared with the normal phenotype (NFR/wr) littermates as well as mice from two related normal mouse strains: the NFR/N parent strain, and the closely related C57B1/6N mouse strain. The immunoreactive (IR) neuronal processes containing TRH appeared in all specimens within Rexed's laminae VIII, IX, and X. Compared with the normal (C57B1/6N, NFR/N) specimens, the pair-matched normal phenotype (NFR/wr) and Wobbler (wr/wr) specimens possessed significantly greater numbers of IR-TRH containing processes at every age studied. Compared with the normal phenotype (NFR/wr) specimens, greater numbers of IR-TRH containing processes appeared in the ventral horn region studied from the Wobbler (wr/wr) specimens taken early (Stage 1) as well as later (Stages 3 and 4) in the motoneuron disease. An age-related decline in the number of IR-TRH processes was apparent among the specimens from the Wobbler mouse strain (NFR/wr, wr/wr), but not the normal (NFR/N, C57B1/6N) mouse strains. The data suggest that TRH may play a significant role in the Wobbler disease, possibly even before the symptoms become apparent. In addition strain-related differences exist which may be important to the etiology of the Wobbler disorder.

Animals↗

Synthesis of 5-methyl-5-deaza nonclassical antifolates as inhibitors of dihydrofolate reductases and as potential antipneumocystis, antitoxoplasma, and antitumor agents.

A series of 2,4-diamino-5-methyl-6-(anilinomethyl)pyrido[2,3-d]pyrimidines 4-9 were synthesized as 5-deaza nonclassical antifolates containing trimethoxy, dichloro-, or trichlorophenyl substitutions and a N-H, N-CH3, or N-CHO at the 10-position. The compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii (P. carinii), Toxoplasma gondii (T. gondii), rat liver (RL), and Lactobacillus casei (L. casei); as inhibitors of T. gondii and P. carinii cell growth in culture; and as antitumor agents. The compounds were prepared by modifications of procedures for classical 5-deaza folates. 2,4-Diamino-5-methyl-6-[(3',4',5'-trimethoxy-N- methylanilino)methyl]pyrido[2,3-d]pyrimidine (5a) exhibited high potency as well as selectivity (compared to RL DHFR) for P. carinii and T. gondii DHFR. Compound 5a is one of the most potent and selective nonclassical folate inhibitors of T. gondii DHFR known. The N-10 formyl analogue 2,4-diamino-5-methyl-6-[(N-formyl-3',4',5'-trimethoxyanilino) methyl]pyrido-[2,3-d]pyrimidine (6a) had decreased potency, but it maintained high selectivity for T. gondii DHFR. The corresponding chloro-substituted analogues maintained potency or had decreased potency; N-10 substitution did not increase potency or selectivity to the extent observed in the 3',4',5'-trimethoxy series. Partial reduction of the B ring to afford the dihydro analogue 2,4-diamino-5-methyl-6-[(N-formyl-3',4',5'-trimethoxyanilino) methyl]-5,8-dihydropyrido[2,3-d]pyrimidine (7), its 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine analogue 8, and 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino)methyl]-5,6,7, 8- tetrahydropyrido[2,3-d]pyrimidine (9) resulted in a significant decrease in potency. In T. gondii cell culture inhibitory studies, 2,4-diamino-5-methyl-6-[(3',4',5'- trimethoxyanilino)methyl]pyrido[2,3-d]pyrimidine (4a), 5a, and 6a were less potent compared to their DHFR inhibitory potencies. Against P. carinii cells in culture, 4a and 5a at 10 micrograms/mL were as effective as the clinically used combination of trimethoprim/sulfamethoxazole (50/250 micrograms/mL). With the exception of the B ring reduced analogues 7-9, all of the compounds were significantly cytotoxic to leukemia CCRF-CEM cells in culture. The chloro-substituted analogues, in general, were more potent against a variety of other tumor cells in culture than the trimethoxy analogues. These results were corroborated by the preclinical tumor screening program at the National Cancer Institute where the most potent compound 2,4-diamino-5-methyl-6-[(3',4'-dichloroanilino)methyl]pyrido[2,3- d]pyrimidine (4b) was found to inhibit the growth of 26 tumor cell lines at an IG50 < 1.00 x 10(-8) M.

Animals↗

Differential tyrosine-specific protein phosphorylation in mouse T lymphocyte subsets. Effect of age.

We have previously reported that activation of normal murine T lymphocytes with either anti-CD3 or Con A leads to increased phosphorylation of three phosphotyrosine-containing proteins with molecular masses of 120, 80, and 40 kDa, that antibody to the alpha beta TCR heterodimer induces phosphorylation of the 120- and 80-kDa species, and that aging impairs phosphorylation of all three substrates. In our study we determine if phosphorylation of these substrates differs among T cell subsets in old and young mice. In young mice, we found that the induced levels of all three phosphorylated substrates, 10 min after addition of the mitogenic stimulus, were significantly higher in CD8 than in CD4 cells for anti-CD3 and Con A stimulation; responses to anti-TCR were also higher in CD8 than in CD4 cells for the 80 kDa, although not the 120-kDa substrate. Aging led to significant declines in the ability to phosphorylate all three substrates in the CD8 population, and also of the 80-kDa substrate in CD4 cells. Comparison of unfractionated CD4 to purified CD4 memory T cells showed that the age-dependent shift from naive to memory T cells could explain the loss with age in p80 phosphorylation, in that memory cells were significantly less able to phosphorylate p80 than were the unseparated CD4 preparations. Phosphorylation of p40 also was significantly lower in CD4 memory cells, as was phosphorylation of p120 in responses to anti-CD3. We conclude that subsets of mouse splenic T cells display different patterns of tyrosine-specific protein phosphorylation in the first 10 min after activation, and that the accumulation of memory T cells with age can account for at least some of the age-dependent decline in tyrosine protein kinase pathways.

Aging↗

Pharmacokinetic-pharmacodynamic modeling of caffeine: tolerance to pressor effects.

We propose a parametric pharmacokinetic-pharmacodynamic model for caffeine that quantifies the development of tolerance to the pressor effect of the drug and characterizes the mean behavior and inter-individual variation of both pharmacokinetics and pressor effect. Our study in a small group of subjects indicates that acute tolerance develops to the pressor effect of caffeine and that both the pressor effect and tolerance occur after some time delay relative to changes in plasma caffeine concentration. The half-life of equilibration of effect with plasma caffeine concentration is about 20 minutes. The half-life of development and regression of tolerance is estimated to be about 1 hour, and the model suggests that tolerance, at its fullest, causes more than a 90% reduction of initial (nontolerant) effect. Whereas tolerance to the pressor effect of caffeine develops in habitual coffee drinkers, the pressor response is regained after relatively brief periods of abstinence. Because of the rapid development and regression of tolerance, the pressor response to caffeine depends on how much caffeine is consumed, the schedule of consumption, and the elimination half-life of caffeine.

Adult↗

Molecular analysis of the Actinobacillus pleuropneumoniae RTX toxin-III gene cluster.

Actinobacillus pleuropneumonia strains that secrete three different exotoxins (ApxI, ApxII, and ApxIII) have been implicated in the etiology of porcine pleuropneumonia. To understand the role of these toxins in the pathogenesis of this disease, we have previously reported the cloning of the hemolysin gene (apxII) (Chang et al., 1989a), which encodes a 110-kD polypeptide with hemolytic and cytotoxic activity. To clone the third toxin gene (apxIII), a new genomic library using A. pleuropneumoniae serotype 2 chromosomal DNA was constructed. A series of five overlapping recombinant phage clones carrying the gene (apxIII) for this 120-kD antigen were identified using a DNA probe containing sequences from the Pasteurella haemolytica lktBD genes. Sequence analysis of a region of the cloned DNA reveals four open reading frames encoding proteins with predicted masses of 20.4, 112.5, 80.3, and 54.7 kD. These genes, designated apxIIC, apxIIIA, apxIIIB, and apxIIID, respectively, are similar in sequence to the RTX (repeat of toxin) toxin family. The toxin produced by the cloned gene kills BL-3 cells and is not hemolytic in vitro.

Actinobacillus pleuropneumoniae↗

Expression of an Atriplex nummularia gene encoding a protein homologous to the bacterial molecular chaperone DnaJ.

DnaJ is a 36-kD heat shock protein that functions together with Dnak (Hsp70) as a molecular chaperone in Escherichia coli. We have obtained a cDNA clone from the higher plant Atriplex nummularia that encodes a 46.6-kD polypeptide (ANJ1) with an overall 35.2% amino acid sequence identity with the E. coli DnaJ. ANJ1 has 43.4% overall sequence identity with the Saccharomyces cerevisiae cytoplasmic DnaJ homolog YDJ1/MAS5. Complementation of the yeast mas5 mutation indicated that ANJ1 is a functional homolog of YDJ1/MAS5. The presence of other DnaJ homologs in A. nummularia was demonstrated by the detection of proteins that are antigenically related to the yeast mitochondrial DnaJ homolog SCJ1 and the yeast DnaJ-related protein Sec63. Expression of the ANJ1 gene was compared with that of an A. nummularia Hsp70 gene. Expression of both ANJ1 and Hsp70 transcripts was coordinately induced by heat shock. However, noncoordinate accumulation of ANJ1 and Hsp70 mRNAs occurred during the cell growth cycle and in response to NaCl stress.

Amino Acid Sequence↗

Molecular characterization of a leukotoxin gene from a Pasteurella haemolytica-like organism, encoding a new member of the RTX toxin family.

A Pasteurella haemolytica-like organism, a new species of bacterium isolated from piglets with diarrhea, secretes a leukotoxin into the culture media. Western blot (immunoblot) analysis indicated that this leukotoxin cross-reacted with antileukotoxin antibody derived from cattle immunized with P. haemolytica. Five overlapping recombinant bacteriophages carrying the gene for this 105-kDa polypeptide were identified with a DNA probe containing sequences from the P. haemolytica lktCA genes from a P. haemolytica-like organism strain 5943 genomic library. Sequence analysis of a region of the cloned DNA revealed two open reading frames encoding proteins with predicted masses of 19.4 and 101.6 kDa. These genes, which we designate pllktC (P. haemolytica-like organism leukotoxin C gene) and pllktA (A gene), respectively, are similar in sequence to the RTX (repeat of toxin) toxin family. The structure of the 101.6-kDa protein derived from the DNA sequence shows three transmembrane domains in the N-terminal part of the protein, 13 glycine-rich repeat domains in the second half of the protein, and a hydrophobic C-terminal part. pllktC and pllktA are strongly homologous to P. haemolytica lktC and lktA genes. However, this leukotoxin kills both BL-3 and pig leukocytes and is not hemolytic.

Amino Acid Sequence↗

[Pheochromocytoma: report of 40 cases].

Forty cases of pheochromocytoma were treated surgically in our hospital from 1965 to 1992. The tumors in the adrenal were noted in 32 cases and outside the adrenal in 8. 38 cases had benign tumors, 1 malignant tumor and 1 sympathetic ganglioma. After the operation, blood pressure normalized in 33 cases and fell obviously but still high in 7 cases. It is a simply selective method for diagnosis of pheochromocytoma by assay of VMA in 24 hours urine sample of the patients with typical clinical symptoms.

Adolescent↗

[Polymerase chain reaction for diagnosis of chronic gonorrhoeae prostatitis].

12 cases of chronic gonorrhoeae prostatitis (CGP) were diagnosed with polymerase chain reaction (PCR). The PCR results were compared with these of culture of prostate fluid (CPF). PCR took 5 hours with a positive rate of 100% and CPF took 3-15 days with a positive rate of 50%. It was shown that PCR is superior to CPF and is a very good method for the diagnosis of CGP.

Adult↗