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Biomedical subjects

J Zhao

Publications and source records attributed to J Zhao.

At least 613 records · Page 34Linked to original sources
PubMed1995

A direct regulatory role for troponin T and a dual role for troponin C in the Ca2+ regulation of muscle contraction.

Troponin (Tn), containing three subunits: Ca2+ binding (TnC), inhibitory (TnI), and tropomyosin binding (TnT), plays a crucial role in the Ca2+ regulation of vertebrate striated muscle contraction. These three subunits function by interacting with each other and with the other thin filament proteins. Previous studies suggested that the primary role of TnT is to anchor the TnI.TnC complex to the thin filament, primarily through its interactions with TnI and tropomyosin. We propose here a new role for TnT. Our results indicate that, when TnT is combined with the TnI.TnC complex, there is an activation of actomyosin ATPase that is Ca(2+)-dependent. To determine whether the latter results from a direct effect of TnC on TnT or indirectly from an effect of TnC on TnI which is transmitted to TnT, we prepared a deletion mutant (deletion of residues 1-57) of TnI, TnId57 (Sheng et al. (1992) J. Biol. Chem. 267, 25407-25413), which interacts with TnC but not TnT. Both wild type (TnI.TnC.TnT) and mutant (TnId57.TnC.TnT) Tn complexes demonstrated equivalent activity in the Ca2+ regulation of actomyosin-S1 ATPase activity. Similarly, both TnI and TnId57 could equally reconstitute TnI-depleted skinned muscle fibers. Therefore, since TnId57 does not interact with TnT, these results suggest that TnT reconstitutes native Ca2+ sensitivity via direct interaction with TnC. Thus Ca2+ binding to TnC would have a dual role: 1) release of the ATPase inhibition by TnI and 2) activation of the ATPase through interaction with TnT.

Animals↗
PubMed1995

Peak bone mass in young women.

Increasing peak bone mineral density (BMD) or content (BMC) in young women may help to reduce the incidence of osteoporosis. Identifying the age when peak bone content or density is attained is essential to develop strategies aimed at optimizing peak BMD and BMC. Total body bone mineral density (TBBMD) and content (TBBMC) were measured by a dual X-ray absorptiometer in healthy females (n = 247, aged 11-32 years). TBBMD and TBBMC were modeled separately as a nonlinear function of age. By age 22.1 +/- 2.5 years, 99% of peak BMD is attained, and by age 26.2 +/- 3.7 years, 99% of peak BMC is attained. Nonlinear relationships between weight and TBBMD or TBBMC were also modeled. In this model, the influence of several parameters, including age, weight, and height, on BMC and BMD were simultaneously assessed. A model with age and weight described the best fit for TBBMD, whereas age, weight, and height described the best fit for total body TBBMC.

Absorptiometry, Photon↗
PubMed1995

Mimosine differentially inhibits DNA replication and cell cycle progression in somatic cells compared to embryonic cells of Xenopus laevis.

The plant amino acid mimosine has been reported to block cell cycle progression and DNA replication in cultured mammalian cells, perhaps by blocking initiation. In this study, we show that mimosine does not block initiation or any other step in DNA replication in embryonic cells of Xenopus laevis. Mimosine does not block DNA replication in cell-free "cycling" extracts of Xenopus eggs, nor does it block M to S phase transition in cell-free egg extracts released from metaphase arrest. Microinjection of mimosine into 4-cell embryos had no visible effect on development during the first 3 days after fertilization. Prior to the midblastula transition, when the cell cycle consists of alternating S and M phases, neither chromosomal DNA replication nor replication of microinjected plasmid DNA were inhibited by mimosine microinjected into cleaving Xenopus embryos. Microinjection of mimosine after the midblastula transition, when large endogenous stockpiles of DNA replication components have begun to be depleted and Xenopus embryonic cells have acquired G1 and G2 phases, still did not inhibit cell cycle progression or DNA replication. In marked contrast, mimosine arrested the growth of proliferating cultured Xenopus kidney epithelial A6 cells near the G1/S boundary. We conclude that mimosine appears to block DNA replication and cell cycle progression in somatic cells, but has no apparent effect in rapidly dividing Xenopus embryonic cells.

Animals↗
PubMed1995

Delayed macular choriocapillary circulation in age-related macular degeneration.

PURPOSE: To investigate the macular choriocapillary circulation (MCC) in eyes with age-related macular degeneration (ARMD) and to correlate these findings with the associated clinical and angiographic drusen characteristics. METHODS: Scanning laser ophthalmoscope fluorescein videoangiography was performed on 34 eyes with age-related macular degeneration and eight age-matched normal volunteers. Drusen characteristics were assessed using the Wisconsin age-related maculopathy grading scale. RESULTS: A delayed macular choriocapillary circulation (DMCC) was defined as a macular choriocapillary filling time greater than 3 standard deviations from the normal mean (greater than 5 seconds). Nine (26%) of the 34 eyes with ARMD were found to have a DMCC. After age adjustment, eyes with DMCC were more likely to have geographic atrophy of the retinal pigment epithelium (p = 0.003) or choroidal neovascularization p = 0.07) than were eyes with a normal MCC. Regional differences in choriocapillary filling times were present in the eyes with a DMCC, including nasal-to-temporal, central-to-peripheral, and inferior-to-superior gradients of progressively less choriocapillary filling delay. The DMCC correlated with the location, number, size, confluence, and fluorescein staining characteristics of the associated drusen. CONCLUSION: DMCC occurs in some eyes with ARMD. This finding may not only assist in defining eyes at risk for progressive disease but may also help to elucidate the pathogenesis of age-related macular degeneration.

Aged↗
PubMed1995

Biological evaluation of epoxy analogs of 1 alpha,25-dihydroxyvitamin D3.

The biological activity of 16-epoxy side-chain analogs of 1 alpha,25-dihydroxyvitamin D3, (1 alpha,25(OH)2D3) was evaluated in vitro and in vivo. Compared to 1 alpha,25(0H)2D3, all analogs had lower affinities for the pig duodenal vitamin D receptor and also for the human serum vitamin D binding protein. The in vitro effects on cell proliferation or differentiation of human promyeloid leukemia (induction of superoxide production in HL-60 cells), human osteosarcoma MG-63 cells (osteocalcin secretion), or human breast cancer cells (incorporation of thymidine in MCF-7 cells), was markedly inhibited by several epoxy analogs, compared to 1 alpha,25(OH)2D3, but the rank order of their activity widely varied among different cancer cells. The most potent analogs (24S,25S-24-hydroxy-25,26-epoxy-22-ene-1 alpha-OHD3, 25,26-epoxy-23-yne-1 alpha-OHD3, and 25,26-epoxy-23-yne-20-epi-1 alpha-OHD3 or compounds, 16, 5, and 7, respectively) were equipotent (16 and 5) or 30-fold (compound 7 on MG-63 cells) to 40-fold (compound 7 on MCF-7 cells) more active than 1 alpha,25-(OH)2D3. These analogs were nevertheless poorly antirachitic (< 3%) when tested in vitamin D-deficient chicks (using serum and bone calcium, serum osteocalcin and duodenal calbindin D-28K, as end points). Compound 7 was also 100-fold more active than 1 alpha,25-(OH)2D3 in inhibition of proliferation of human foreskin keratinocytes. Some epoxy analogs of 1 alpha,25-(OH)2D3 thus display interesting dissociations between their receptor affinity and their potency to induce cell differentiation, whereas their effect on cell proliferation/differentiation exceed their calcemic effects more than 100- to 1000-fold.

Animals↗
PubMed1995

Antagonistic activity of 24-oxa-analogs of vitamin D.

24-Oxa-vitamin D3 (24-oxa-D3) and 24-oxa-1 alpha-hydroxyvitamin D3 were designed as possible inhibitors of the vitamin D metabolic activation pathway. Their affinity for the vitamin D receptor (from pig intestine) and human vitamin binding protein were reduced, and their potency to induce cell differentiation of human leukemia cells (HL 60) or osteosarcoma cells (MG 63) was markedly reduced (19% and 3%, respectively), in comparison with calcitriol. A single or chronic injection of 24-oxa-D3 had no biological activity, whereas chronic administration of 24-oxa-1 alpha-hydroxy-D3 showed weak agonist activity in rachitic chicks. When the 24-oxa-D3 was given prior to a single injection of vitamin D3, lower values of serum calcium (64% of the value obtained in vitamin D-treated animals), osteocalcin (52%), 25-(OH)D3 (45%) and duodenal calbindin-D 28K (9.4%) were found. When given chronically in a 100-fold more excess no clear antagonistic effects were observed. 24-Oxa-D3 is thus a new metabolic weak antagonist of vitamin D3, but adding a hydroxyl group at C-1 creates a weak agonist.

Animals↗
PubMed1995

Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene isolation and expression and characterization of the enzyme.

The gene encoding the bifunctional dihydrofolate reductase (DHFR) and thymidylate synthase (TS) of Trypanosoma brucei brucei has been isolated and expressed in Escherichia coli, and the enzyme has been purified and characterized. The coding sequence of the DHFR-TS is 1581 nt, encoding a 527-amino-acid protein of 58,505 Da. The gene was expressed under control of the trc promoter in pKK233-2. The resulting expression plasmid conferred trimethoprim resistance to E. coli DH5 alpha and complemented the TS deficiency in chi 2913recA cells indicating the presence of active DHFR and TS. DHFR-TS was purified by methotrexate-Sepharose chromatography. In addition to the full-length enzyme, the purified enzyme contained 31 and 31.5-kDa forms of the enzyme that cross-reacted with anti-L. major DHFR-TS antibodies; one was truncated at the N- and C termini, and the other at only the C terminus. Despite the presence of sufficient TS for complementation, TS activity was not detectable in the crude extract or in the final purified enzyme preparation. Although the majority of the enzyme appears to be full length, it is possible that the TS domain has been degraded by one of more residues, which would inactivate the ability to synthesize thymidylate. Kinetic analysis of DHFR yielded kcat and Km values similar to those of related enzymes. The T. brucei DHFR has Ki values for antimicrobial antifolates pyrimethamine and trimethoprim which are significantly lower than the closely related T. cruzi or L. major DHFRs or than human DHFR.

Amino Acid Sequence↗
PubMed1995

The rise and prospects of medical aesthetics.

Since the 1980s, Chinese scholars have been trying to expound and synthetise elementary aesthetical ideas which occur in medicine, in order to treat this area of study as a defined branch of medicine--'medical aesthetics'. It is in this context that the points discussed in this paper arise. We set forth in detail the ideas, objectives and methods adopted within the framework of medical aesthetics and its applied branch--medical cosmetology and expound the relations between them. We think the task of medical aesthetics is to study the human body in its entirety, concentrating on both internal and external beauty and put the findings into practice, whereas the task of medical cosmetology is to study and assess only the external beauty of the human body and to take action on that basis. Medical cosmetology is the enforcement of medical aesthetics, practised in order to give positive results connected with physical beauty, and is therefore easily understood by the layman. It is known that the development of medical cosmetology represents an important breakthrough in the development of medical aesthetics. We think that beauty should not be measured mechanically, always following the same pattern, but that it should be considered individually with everyone's own particular characteristics. The quality of physical attractiveness should be assessed jointly by the doctor and his patient or client, not solely by either of these individuals nor even by a group of doctors.(ABSTRACT TRUNCATED AT 250 WORDS)

China↗
PubMed1995

Darwin's selection within the human body.

It has been widely accepted that Darwin's natural selection plays a basic role in carcinogenesis and some other disease processes, but is not relevant to the normal multicellular life within the human body. The hypothesis proposed here is that selection and other evolutionary mechanisms not only normally or physiologically exist within the body of human beings and other multicellular organisms, but also persist and 'function' throughout the entire life span of the organism, from the embryo development to the aging process. This is based on the concept of cell individuality and the fact that there are a great deal of variations in cell populations, in particular possible existence of somatic genetic variations within the body. To realize the existence of natural selection in the multicellular life and study how it operates within organisms in both physiological and pathological conditions are fundamentally important to our understanding of human biology and medicine.

Cell Division↗
PubMed1995

Cell individuality: a basic multicellular phenomenon and its role in the pathogenesis of disease.

Every type of cell has its own special features that differentiate its members qualitatively from cells of other types. Within the same type of cells, however, every single cell also has its own unique characteristics that deviate itself from other individual cells, although they are alike collectively. These kinds of individual differences between cells are described here as cell individuality, which says basically that, within a cell population or even within a multicellular organism, every cell is a unique individual living being; and no single cell could be completely identical to another, regardless of how similar to each other they are. The individuality of a single cell can be represented by all sorts of cell characteristics, which are countless and range from physiological activities to molecular constituents. These individual differences in cell characteristics are generally presented much more in degree or in quantity, rather than in kind or in quality. Moreover, such cell individuality or quantitative variations within or even between cell populations may also play a basic role in the pathogenesis of disease, and particularly in the susceptibility of cells to the disease process.

Cell Physiological Phenomena↗
PubMed1995

Multi-organ donor transmission of hepatitis C virus to five solid organ transplant recipients and lack of transmission to corneal transplant recipients.

BACKGROUND: A multi-organ donor seronegative for hepatitis C virus (HCV) by 1st generation enzyme immunoassay (EIA) supplied 5 solid organs and 2 corneas to 7 recipients. This donor was retrospectively shown to be 2nd generation HCV EIA-positive and polymerase chain reaction (PCR)-positive. All 5 solid organ recipients but none of the corneal recipients developed HCV infection. OBJECTIVES: To demonstrate the discordance between serological and PCR-based HCV detection in solid organ transplant recipients and the lack of transmission of HCV to the two corneal transplant recipients. STUDY DESIGN: All 5 solid organ recipients were retrospectively shown to be HCV PCR-negative and -seronegative pre-transplant and HCV PCR-positive post-transplant. Serial serum samples on 3 recipients were evaluated by 2nd generation EIA, a prototypic structural and non-structural dual bead assay (EIA-SA, Abbott), the Chiron Recombinant Immunoblot Assay, 2nd generation (RIBA-2), and the Chiron RIBA HCV Test System Strip Immunoblot Assay 3.0 (RIBA-3, Chiron). RESULTS: The dual bead EIA-SA and RIBA-3 were able to detect HCV seroconversion approximately 6 months earlier than the 2nd generation EIA in 2 recipients, and in 1 recipient only PCR detected infection within the first 10 months. There was no evidence of HCV transmission to the corneal recipients. CONCLUSIONS: Although third generation assays such as the RIBA-3 and EIA-SA narrowed the window of HCV seronegativity in transplant recipients compared with the 2nd generation EIA, PCR was the most sensitive method of detecting acute HCV infection. Despite transmission of HCV to all of the solid organ recipients HCV was not transmitted to the corneal transplant recipients.

Journal Article↗
PubMed1995

Rectification of skeletal muscle ryanodine receptor mediated by FK506 binding protein.

The cytosolic receptor for immunosuppressant drugs, FK506 binding protein (FKBP12), maintains a tight association with ryanodine receptors of sarcoplasmic reticulum (SR) membrane in skeletal muscle. The interaction between FKBP12 and ryanodine receptors resulted in distinct rectification of the Ca release channel. The endogenous FKBP-bound Ca release channel conducted current unidirectionally from SR lumen to myoplasm; in the opposite direction, the channel deactivated with fast kinetics. The binding of FKBP12 is likely to alter subunit interactions within the ryanodine receptor complex, as revealed by changes in conductance states of the channel. Both on- and off-rates of FKBP12 binding to the ryanodine receptor showed clear dependence on the membrane potential, suggesting that the binding sites of FKBP12 reside in or near the conduction pore of the Ca release channel. Rectification of the Ca release channel would prevent counter-current flow during the rapid release of Ca from SR membrane, and thus may serve as a negative feedback mechanism that participates in the process of muscle excitation-contraction coupling.

Animals↗
PubMed1995

5-Fluoroindole resistance identifies tryptophan synthase beta subunit mutants in Arabidopsis thaliana.

A study of the biochemical genetics of the Arabidopsis thaliana tryptophan synthase beta subunit was initiated by characterization of mutants resistant to the inhibitor 5-fluoroindole. Thirteen recessive mutations were recovered that are allelic to trp2-1, a mutation in the more highly expressed of duplicate tryptophan synthase beta subunit genes (TSB1). Ten of these mutations (trp2-2 through trp2-11) cause a tryptophan requirement (auxotrophs), whereas three (trp2-100 through trp2-102) remain tryptophan prototrophs. The mutations cause a variety of changes in tryptophan synthase beta expression. For example, two mutations (trp2-5 and trp2-8) cause dramatically reduced accumulation of TSB mRNA and immunologically detectable protein, whereas trp2-10 is associated with increased mRNA and protein. A correlation exists between the quantity of mutant beta and wild-type alpha subunit levels in the trp2 mutant plants, suggesting that the synthesis of these proteins is coordinated or that the quantity or structure of the beta subunit influences the stability of the alpha protein. The level of immunologically detectable anthranilate synthase alpha subunit protein is increased in the trp2 mutants, suggesting the possibility of regulation of anthranilate synthase levels in response to tryptophan limitation.

Alleles↗
PubMed1995

Arabidopsis phosphoribosylanthranilate isomerase: molecular genetic analysis of triplicate tryptophan pathway genes.

Phosphoribosylanthranilate isomerase (PAI) catalyzes the third step of the tryptophan biosynthetic pathway. Arabidopsis PAI cDNAs were cloned from a cDNA expression library by complementation of an Escherichia coli trpC- PAI deficiency mutation. Genomic DNA blot hybridization analysis detected three nonallelic genes encoding PAI in the Arabidopsis genome. DNA sequence analysis of cDNA and genomic clones indicated that the PAI1 and PAI2. All three PAI polypeptides possess an N-terminal putative plastid target sequence, suggesting that these enzymes all function in plastids. The PAI1 gene is flanked by nearly identical direct repeats of approximately 350 nucleotides. Our results indicate that, in contrast to most microorganisms, the Arabidopsis PAI protein is not fused with indole-3-glycerolphosphate synthase, which catalyzes the next step in the pathway. Yeast artificial chromosome hybridization studies indicated that the PAI2 gene is tightly linked to the anthranilate synthase alpha subunit 1 (ASA1) gene on chromosome 5. PAI1 was mapped to the top of chromosome 1 using recombinant inbred lines, and PAI3 is loosely linked to PAI1. cDNA restriction mapping and sequencing and RNA gel blot hybridization analysis indicated that all three genes are transcribed in wild-type plants. The expression of antisense PAI1 RNA significantly reduced the immunologically observable PAI protein and enzyme activity in transgenic plants. The plants expressing antisense RNA also showed two phenotypes consistent with a block early in the pathway: blue fluorescence under UV light and resistance to the anthranilate analog 6-methylanthranilate. The extreme nucleotide conservation between the unlinked PAI1 and PAI2 loci suggests that this gene family is actively evolving.

Aldose-Ketose Isomerases↗
PubMed1995

Inhibitory action of metabolites of Pseudomonas aeruginosa against gram-negative bacteria.

Fifty clinical isolates of Pseudomonas aeruginosa were tested for inhibition of growth of clinical isolates of Escherichia coli, Salmonella infantis, Klebsiella pneumoniae and other Gram-negative bacteria in the authors' laboratory. Pseudomonas aeruginosa was strongly active against both E. coli and Enterobacter cloacae, with 89.4% and 94.7% inhibition respectively, but weakly active against S. infantis, K. pneumoniae and Proteus mirabilis with 56.3%, 48.8% and 23.8% inhibition, respectively. The pigmented strains were found to have stronger antimicrobial activity than the unpigmented strains. Pyocyanin, the major metabolite of Pseudomonas aeruginosa, has been shown to inhibit Escherichia coli, Proteus spp. and other Gram-negative bacteria, by research with a few strains of P. aeruginosa and a single inhibited strain. However, little attempt has been made to determine the inhibitory action of many strains of P. aeruginosa against a large number of clinical isolates such as Escherichia spp., Klebsiella spp., and Salmonella spp., up to now. For this reason, in this study we examined 50 randomly selected clinical isolates of P. aeruginosa for inhibition of growth of a wide range of Gram-negative bacteria, including 30 strains of E. coli, 30 of K. pneumoniae, 30 of S. infantis, 6 of Enterobacter cloacae and 9 of Proteus mirabilis.

Antibiosis↗
PubMed1995

Mechanisms of conduction time hysteresis in rabbit atrioventricular node.

The functional origin of atrioventricular nodal hysteresis was studied in isolated rabbit heart preparations. This hysteresis is characterized by asymmetric changes in nodal conduction time (NCT) occurring for symmetric changes in cycle length. The respective contribution of the nodal properties of recovery, facilitation, and fatigue to the beat-to-beat changes in NCT observed during paired symmetric ramps of decreasing and increasing cycle length was determined with specifically design stimulation protocols. Nodal hysteresis was found to be entirely accounted for by variations in the contribution of nodal recovery and fatigue properties observed at corresponding cycle lengths. The study establishes how this contribution varies on a beat-to-beat basis as a result of cycle length history. This holds true for the numerous changes in hysteresis observed in response to changes in the sequence and slope of the ramps. Facilitation clearly affected NCT during these responses but did not contribute to the hysteresis. Moreover, the study demonstrates that there is no inherent change in the characteristics of nodal function with the direction of the ramp that could account for the hysteresis. Thus nodal hysteresis arises from nodal functional properties of recovery and fatigue but does not constitute a distinct independent intrinsic property of the node.

Animals↗
PubMed1995

Cardiac troponin I phosphorylation increases the rate of cardiac muscle relaxation.

Cardiac troponin (Tn) I (CTnI), compared with skeletal TnI, contains extra amino acids (32 to 33) at its amino terminus, including two adjacent serine residues. These two serine residues are believed to be phosphorylated by protein kinase A (PKA) upon stimulation of the heart by beta-agonists. In this study, we found that phosphorylation of a cardiac skinned muscle preparation by PKA, mainly at CTnI, results in a decrease in the Ca2+ sensitivity of muscle contraction. The pCa50 decreased by approximately 0.27 +/- 0.06 pCa units upon phosphorylation. To study cardiac muscle relaxation, we used diazo-2, a photolabile Ca2+ chelator with a low Ca2+ affinity in its intact form that is converted to a high-affinity form after photolysis. We found that the rate of cardiac muscle relaxation increased from a time of half-relaxation (t1/2) = 110 +/- 10 milliseconds to t1/2 = 70 +/- 8 milliseconds after CTnI phosphorylation. This result demonstrates that CTnI phosphorylation can be linked with the increased rate of muscle relaxation in a relatively intact muscle preparation. Since CTnI phosphorylation has been shown previously to affect the Ca2+ affinity and Ca2+ off-rate of CTnC in vitro, it is likely that the faster relaxation seen here reflects faster dissociation of Ca2+ from cardiac TnC (CTnC). Model calculations show that increased dissociation of Ca2+ from CTnC, coupled with the faster uptake of Ca2+ by the sarcoplasmic reticulum stimulated by PKA phosphorylation of phospholamban, can account for the faster relaxation seen in the inotropic response of the heart to catecholamines.

Adenosine Triphosphatases↗