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Biomedical subjects

B Zhao

Publications and source records attributed to B Zhao.

At least 217 records · Page 12Linked to original sources

Biochemical hyperparathyroidism and bone mineral status in patients treated long-term with lithium.

Lithium is known to interfere with normal calcium homeostasis, but the long-term effects and possible clinical significance are uncertain. Thus, we measured indices of parathyroid function including intact parathyroid hormone (PTH) and ionized and total calcium levels in 26 patients treated for manic-depressive psychosis with lithium for 10 years or longer (mean +/- SD duration, 15 +/- 6 years). Increased ionized calcium levels were found in 11 patients and increased PTH concentrations in five patients. Altogether, 54% of the patients (14 of 26) had ionized calcium and/or PTH levels above the laboratory reference range. The PTH/ionized calcium relationship of the lithium-treated patients was compared with that of a group of normal subjects (n = 23) and with those of three different groups of patients with abnormal parathyroid function (chronic hypoparathyroidism, n = 21; primary hyperparathyroidism [HPT], n = 50; and tertiary HPT, n = 21). Lithium-treated patients had significantly higher ionized calcium levels (P < .0001) but not significantly higher PTH concentrations (P = .08) than the normal subjects. In comparison to the normal controls, lithium-treated patients had a right-sided shift in their PTH/ionized calcium relationship that was in the same direction but less prominent than in primary or tertiary HPT. Dual-energy x-ray absorptiometry disclosed similar bone mineral densities (BMDs) of lithium-treated patients and age-, sex-, and body mass-matched normal controls in the whole body, lumbar spine, and femoral neck (Z scores: +1.20, +1.22, and +1.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A new class of noninactivating K+ channels from aplysia capable of contributing to the resting potential and firing patterns of neurons.

From the nervous system of Aplysia, we have cloned a new class of noninactivating K+ channels (aKv5.1) that are activated at low voltage and are capable of contributing to the resting potential and firing patterns of neurons. Expression of aKv5.1 in Aplysia neuron R15 revealed that aKv5.1 exerts an unusual control over cell excitability; it increased the resting potential by more than 20 mV and abolished the spontaneous bursting activity of the cell. In its ability to suppress the endogenous rhythm of R15, aKv5.1 differs in its actions from transient, inactivating K+ channels such as aKv1.1a, an Aplysia homolog of Shaker. aKv1.1a shortens the duration of the spike and increases the afterpotential, but does not suppress bursting. Thus, by expressing different classes of K+ channels, it is possible to redesign, in specific ways, the signaling capabilities of specific, identified neurons.

Action Potentials↗

Platelet-activating factor acetylhydrolase in term and preterm human milk: a preliminary report.

Human milk may protect against necrotizing enterocolitis (NEC). Since platelet-activating factor (PAF) may participate in the pathophysiology of NEC, we measured PAF acetylhydrolase (PAF-AH), which metabolizes PAF, in term and preterm human milk. The activity of PAF-AH in term milk collected 2-4 days after delivery (n = 17) was 2.7 +/- 1.2 nmol x min-1 x ml-1. A higher activity was found in milk collected at similar times from mothers who delivered between 33 and 36 weeks of gestation (n = 6, 5.6 +/- 2.1 nmol x min-1 x ml-1, p < 0.01). However, milk from mothers who delivered between 26 and 32 weeks of gestation had a PAF-AH activity similar to that of term milk (n = 6, 3.0 +/- 0.7 nmol x min-1 x ml-1). With advancing lactational age, PAF-AH activity in term milk decreased, whereas the activity of this enzyme in preterm milk remained unchanged. In milk samples collected beyond 14 days after delivery from women who gave birth between 33 and 36 weeks or 26 and 32 weeks of gestation, PAF-AH activity was fivefold higher than that found in milk for women delivering at term (3.7 +/- 1.3 and 3.6 +/- 3.6 nmol x min-1 x ml-1 serum 0.7 +/- 0.4 nmol x min-1 x ml-1, respectively, p < 0.05). We speculate that the presence of PAF-AH in human milk may protect against NEC in preterm newborns.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Brain abscess due to Pasteurella multocida.

The patient was a 26-year-old man who complained of headache and vomiting. On examination, there was nothing abnormal, but the edge of the right optic papilla was not clear. His temperature was 38.5 degrees C, pulse 96/min, blood pressure 120/80 mmHg. A space-occupying lesion in his fronto-dextra cupular part was found by CT scanning. He had a 12-year history of chronic purulent otitis. The diagnosis was a brain abscess in the fronto-dextra cupular part. The brain abscess was extracted and Pasteurella multocida was isolated from the dark brown pus draining from the abscess. The patient recovered through proper antibiotic therapy based on a sensitivity test. Reports of infections caused by this organism in foreign countries very widely from local infections due to bites and scratches by cats, dogs etc. to general infections such as infections of the respiratory tract, sepsis and meningitis. However, Pasteurella multocida brain abscesses are rare. Pasteurella multocida is a Gram-negative short rod which is best known as part of the mouth flora and as a pathogen causing septicemia in many domestic animals, such as cats, dogs etc.. Infection in man results mainly from animal bites or scratches. It has been reported that Pasteurella multodida can cause human septicemia, meningitis, respiratory tract infection, conjunctivitis and other infections. We isolated a strain of Pasteurella multocida from the pus of a brain abscess following chronic purulent otitis on August 6, 1990.

Adult↗

Detection of free radicals by electron spin resonance in rat diaphragm after resistive loading.

Indirect evidence supports free radical production in the diaphragm under excessive mechanical loads in both in vitro and in situ preparations. We hypothesized that free radicals are produced in the diaphragm with loads in vivo at a sufficient concentration to be detected by electron spin resonance (ESR) spectroscopy. Anesthetized rats underwent severe inspiratory resistive loading for 2.5-3 h with maintenance of blood oxygenation and arterial blood pressure by breathing 70% oxygen. The ESR spectra of four samples (freeze-clamped at liquid nitrogen temperature) from each experimental animal were compared with the spectra from a control animal breathing air and a control animal breathing 70% oxygen. We observed 1) an approximately 30% increase in intensity of free radical signal in experimental animals (n = 10) compared with control animals breathing oxygen (n = 10; P < 0.01) and control animals breathing air (n = 10; P < 0.05), 2) that oxygen alone had no effect on the ESR spectrum, and 3) the intensity of the ESR signal decreased approximately 25% in the experimental group when samples were taken 10 min postmortem, whereas no difference in signal was observed for control animals. We conclude that the diaphragm shows an increased production of free radicals associated with respiratory failure induced by resistive breathing.

Animals↗

[Clinical study of the treatment of fallopian tube obstruction with catheter recanalization and blood stasis removing drugs].

50 patients with fallopian tube obstruction were initially treated by catheter recanalization, and then randomly divided into two groups. Chinese medicine group (CMG) treated with Tongjingbao and Angelicae Complex Injection and Western medicine (Gentamycin, Dexamethasone, Chymotrypsin) group (WMG) as a control. The course of treatment was three months. Before and after treatment, the hemorheology change was analysed. After treatment, all patients except subsequent pregnancy were repeatedly performing hysterosalpingography. The results showed effective rate of recanalization was 94%; corrected pregnancy rate was 100% in CMG and 50% in WMG; the reocclusion rate of fallopian tube was 9% in CMG and 25% in WMG (P < 0.05). The difference of hemorheology change between two groups was significant (P < 0.01) and it was also different before and after treatment in CMG (P < 0.01). This study showed that catheter recanalization was effective in recanalizing the mechanical occluded fallopian tube. The Chinese medicine would inhibit the reocclusion and re-adhesion of tube.

Adult↗

Some humoral factors and their interaction on acute hypoxic pulmonary pressor response.

To determine the effect of humoral factors and their interaction on the development of acute hypoxic pulmonary pressor response (HPPR), we performed studies in 16 mongrel dogs. We measured plasma levels of noradrenaline (NE), angiotensin II (AII), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6KPGF1 alpha), thromboxane B2 (TXB2), leukotriene B4 (LTB4) and 5-hydroxytryptamine (5-HT) before, during and after HPPR. Multiple regression analysis showed that the changes of pulmonary arterial systolic pressure (PASP) and pulmonary arterial diastolic pressure (PADP) correlated well with those of plasma concentration of NE, PGF2 alpha and 6KPGF1 alpha, respectively (r were equal to 0.633 and 0.668, respectively, P < 0.01). The results of orthogonal experiment analysis with an injection of exogenous NE, PGF2 alpha and PGI alpha into main pulmonary artery of dogs showed that NE and the interaction of PGF2 alpha and PGI2 alpha increased PASP (P < 0.05) and PGI2 attenuated PASP (P < 0.01). The interaction of PGF2 alpha and PGI2 and of PGF2 alpha and NE increased PADP(P < 0.01) and PGI2 attenuated PADP (P < 0.01).

6-Ketoprostaglandin F1 alpha↗

Three-dimensional structure of a simian immunodeficiency virus protease/inhibitor complex. Implications for the design of human immunodeficiency virus type 1 and 2 protease inhibitors.

Simian immunodeficiency virus (SIV) proteins have considerable amino acid sequence homology to those from human immunodeficiency virus (HIV); thus monkeys are considered useful models for the preclinical evaluation of acquired immune deficiency syndrome (AIDS) therapeutics. We have crystallized and determined the three-dimensional structure of SIV protease bound to the hydroxyethylene isostere inhibitor SKF107457. Crystals of the complex were grown from 25-32% saturated sodium chloride, by the hanging drop method of vapor diffusion. They belong to the orthorhombic space group I222, with a = 46.3 A, b = 101.5 A, and c = 118.8 A. The structure has been determined at 2.5-A resolution by molecular replacement and refined to a crystallographic discrepancy factor, R (= sigma parallel Fo magnitude of - magnitude of Fc parallel/sigma magnitude of Fo magnitude of), of 0.189. The overall structure of the complex is very similar to previously reported structures of HIV-1 protease bound to inhibitors. The inhibitor is bound in a conformation that is almost identical to that found for the same inhibitor bound to HIV-1 protease, except for an overall translation of the inhibitor, varying along the backbone atoms from about 1.0 A at the termini to about 0.5 A around the scissile bond surrogate. The structures of the SIV and HIV-1 proteins vary significantly only in three surface loops composed of amino acids 15-20, 34-45, and 65-70. Superposition of the 1188 protein backbone atoms from the two structures gives an rms deviation of 1.0 A; this number is reduced to 0.6 A when atoms from the three surface loops are eliminated from the rms calculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Influence of low density lipoproteins on cytosolic free Ca2+ concentration and dense tubular system in human platelets.

The cytosolic free Ca2+ concentration [Ca2+]i and dense tubular system (DTS) of washed human platelets were affected by low density lipoproteins (LDL) of 25 micrograms/ml at 37 degrees C for 10 minutes. After the incubation with LDL, the [Ca2+]i increased from 115 +/- 29 nM to 141 +/- 24 nM. LDL promoted the increase of [Ca2+]i (471 +/- 31 nM) induced by thrombin (0.03 U/ml) as compared to that which thrombin did alone (240 +/- 11 nM) (p < 0.05). The increased Ca2+ influx from the extracellular space is thought to be the reason of the increase in [Ca2+]i, since the effect of LDL was abolished by removal of external Ca2+ by EGTA. The DTS changed primarily from thin elongated forms to rounded vesicles. No evidence was noticed that LDL caused a mobilization of Ca2+ from the DTS.

Biological Transport↗

Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis.

The human immunodeficiency virus type 1 (HIV-1) protease is a potential target of acquired immune deficiency syndrome (AIDS) therapy. A highly potent, perfectly symmetrical phosphinate inhibitor of this enzyme, SB204144, has been synthesized. It is a competitive inhibitor of HIV-1 protease, with an apparent inhibition constant of 2.8 nM at pH 6.0. The three-dimensional structure of SB204144 bound to the enzyme has been determined at 2.3-A resolution by X-ray diffraction techniques and refined to a crystallographic discrepancy factor, R (= sigma parallel F(o) magnitude to - Fc parallel/sigma magnitude of F(o)), of 0.178. The inhibitor is held in the enzyme active site by a set of hydrophobic and hydrophilic interactions, including an interaction between Arg8 and the center of the terminal benzene rings of the inhibitor. The phosphinate establishes a novel interaction with the two catalytic aspartates; each oxygen of the central phosphinic acid moiety interacts with a single oxygen of one aspartic acid, establishing a very short (2.2-2.4 A) oxygen-oxygen contact. As with the structures of penicillopepsin bound to phosphinate and phosphonate inhibitors [Fraser, M. E., Strynadka, N. C., Bartlett, P. A., Hanson, J. E., & James, M. N. (1992) Biochemistry 31, 5201-14], we interpret this short distance and the stereochemical environment of each pair of oxygens in terms of a hydrogen bond that has a symmetric single-well potential energy curve with the proton located midway between the two atoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Platelet-activating factor in surfactant preparations.

Surfactant administration is used for treatment of neonatal respiratory distress syndrome. We studied whether currently used surfactant preparations contain platelet-activating factor (PAF), a potent lipid mediator produced by fetal lungs. Three surfactant preparations from animal sources contained between 36 and 218 pmol of PAF per mL, whereas PAF was undetectable in an artificial surfactant. Based on current recommendations, about 144-654 pmol PAF would be administered per dose of natural surfactant, sufficient to exert possible physiological effects on the lung. The action of PAF may be exacerbated by low activity of PAF-acetylhydrolase, which inactivates PAF, in tracheal fluid from infants with respiratory distress syndrome.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells.

The RRR-alpha-tocopheryl succinate form of vitamin E inhibits the proliferation of estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines in a dose-dependent manner in vitro. Analyses of cell-conditioned medium from RRR-alpha-tocopheryl succinate growth-inhibited cells revealed the presence of a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of the TGF-beta-responsive Mv1Lu-CCL-64 mink lung and murine CTLL-2 cell lines, 2) combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, and 3) neutralization of the antiproliferative activity in the conditioned media by antibodies specific for TGF-beta.

Antioxidants↗

[Study on the induction of active immunity in human by injecting human anti-HBs antibodies].

One hundred and three health volunteers were injected with various doses of human anti-HBs (Ab1). The anti-idotypic antibodies (Ab2) and anti-antiidiotypic antibodies (Ab)3 in sera were tested at intervals of 30 days with ELISA. We found that the dynamic changes between Ab2 and Ab3 of immune sera were cyclical by way of their interaction and the Ag-specific Ab3 were the same as Ab1 in specificity. The results reconfirmed that exogenous human anti-HBs could induce active immunity by activation of idiotypic network and regulation in human body suggesting that injection of Ig into body could bring about not only passive immunity but also active immunity.

Adolescent↗

Structure of scorpion toxin variant-3 at 1.2 A resolution.

The crystal structure of the variant-3 protein neurotoxin from the scorpion Centruroides sculpturatus Ewing has been refined at 1.2 A resolution using restrained least-squares. The final model includes 492 non-hydrogen protein atoms, 453 protein hydrogen atoms, eight 2-methyl-2,4-pentanediol (MPD) solvent atoms, and 125 water oxygen atoms. The variant-3 protein model geometry deviates from ideal bond lengths by 0.024 A and from ideal angles by 3.6 degrees. The crystallographic R-factor for structure factors calculated from the final model is 0.192 for 17,706 unique reflections between 10.0 to 1.2 A. A comparison between the models of the initial 1.8 A and the 1.2 A refinement shows a new arrangement of the previously poorly defined residues 31 to 34. Multiple conformations are observed for four cysteine residues and an MPD oxygen atom. The electron density indicates that disulfide bonds between Cys12 and Cys65 and between Cys29 and Cys48 have two distinct side-chain conformations. A molecule of MPD bridges neighboring protein molecules in the crystal lattice, and both MPD enantiomers are present in the crystal. A total of 125 water molecules per molecule of protein are included in the final model with B-values ranging from 11 to 52 A2 and occupancies from unity down to 0.4. Comparisons between the 1.2 A and 1.8 A models, including the bound water structure and crystal packing contacts, are emphasized.

Amino Acid Sequence↗

The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat.

The effects of the enantiomers of ibuprofen (0.25 and 0.50 mmol/kg b.w.) and flurbiprofen (0.01, 0.03, and 0.06 mmol/kg b.w.) on the beta-oxidation of palmitate were investigated in the rat. The mean cumulative exhalation of 14CO2 after ip administration of [U-14C]palmitic acid was significantly reduced over 6 h by ibuprofen at the higher dose but not at the lower dose for either enantiomer. There was no difference between the enantiomers, the reduction over 6 h being 31.3 and 33.0% for (R)- and (S)-ibuprofen, respectively. There was also a significant inhibition of beta-oxidation by flurbiprofen at all 3 doses. Again, there was no stereoselectivity evident in this inhibition. Flurbiprofen was much more potent than ibuprofen in eliciting this effect, the 0.01mmol/kg dose giving a similar reduction in beta-oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo beta-oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A-dependent mechanism.

Animals↗