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Biomedical subjects

Z Lu

Publications and source records attributed to Z Lu.

At least 361 records · Page 20Linked to original sources
PubMed1995

Structure and function in rhodopsin. Separation and characterization of the correctly folded and misfolded opsins produced on expression of an opsin mutant gene containing only the native intradiscal cysteine codons.

Previous mutagenesis studies have indicated the requirement of a tertiary structure in the intradiscal region with a disulfide bond between Cys-110 and Cys-187 for the correct assembly and/or function of rhodopsin. We have now studied a rhodopsin mutant in which only the natural intradiscal cysteines at positions 110, 185, and 187 are present while all the remaining seven cysteines in the wild-type bovine rhodopsin have been replaced by serines. The proteins formed on expression of this mutant in COS-1 cells bind 11-cis-retinal only partially to form the rhodopsin chromophore. We show that this is due to the presence of both correctly folded chromophore-forming opsin and misfolded opsins. Methods have been devised for the separation of the correctly folded and misfolded forms by selective elution from immunoaffinity adsorbants. Using several criteria, which include SDS-PAGE as well as UV/visible and CD spectroscopy, we find that the correctly folded mutant protein is indistinguishable in its spectral properties from the wild-type rhodopsin. Further, reaction of sulfhydryl groups in the correctly folded mutant pigment with N-ethylmaleimide indicates that alkylation of a single sulfhydryl requires denaturation or illumination, while reaction with an additional two sulfhydryl groups occurs only after reduction. The misfolded mutant opsins are characterized by reduced alpha-helical content, sulfhydryl reactivity under native conditions in the dark, and also the presence of a disulfide bond.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Analysis of 45 kb of DNA located at the left end of the chlorella virus PBCV-1 genome.

Forty-five kilobases of DNA, including the previously sequenced 2.2-kb inverted repeat region, located at the left termini of the 330-kb Chlorella virus PBCV-1 genome were sequenced and analyzed. Eighty-five complete open reading frames (ORFs) larger than 195 nucleotides were identified. Thirty-seven of the 85 ORFs, which are densely packed on both strands of the DNA, were considered major ORFs. Fifteen of the major ORFs have similarity to genes in the databases, including bacterial glycerophosphoryl diester phosphodiesterase, bacteriophage T4 endonuclease V, D-isomer specific 2-hydroxyacid dehydrogenases, and beta-alanine synthetase and bacterial nitrilases. Two major ORFs resemble the virus major capsid protein. Three major ORFs contain three or more ankyrin-like repeat elements and four ORFs encode proline-rich proteins.

Amino Acid Sequence↗
PubMed1995

Development of a parenterally administrable hydrosol preparation of the "third generation platinum complex" [(+/-)-1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II). Part 1. Preparation and studies on the stability and antitumor activity.

The development of a galenical formulation for poorly water soluble dichloroplatinum(II) complexes suitable for the parenteral administration in cancer chemotherapy is described. The procedure, which we elaborated for [(+/-)-1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) (rac-4F-PtCl2), is based on the reaction of a soluble diaquaplatinum(II) salt with sodium chloride in water in the presence of pluronic F 68 as stabilizer and results in a sufficiently stable colloidal solution (i.e. hydrosol). In contrast to the poorly water soluble synthetic rac-4F-PtCl2, which was ineffective towards the hormone sensitive MXT-M-3.2 breast cancer of the mouse, its hydrosol formulation proved to be highly active and was very well tolerated.

Animals↗
PubMed1995

Rat tail suspension reduces messenger RNA level for growth factors and osteopontin and decreases the osteoblastic differentiation of bone marrow stromal cells.

We previously reported that bone marrow stromal cells produce insulin-like growth factors (IGF-I and -II), and that medium conditioned by marrow stromal cells stimulates osteoblast proliferation in vitro. The present study employed the rat tail-suspension model to unload the hindlimbs. It was designed to test the hypothesis that the development of osteopenia or osteoporosis could be due to a deficit in the osteogenic function of marrow stromal cells. Although tail suspension suppressed body weight during the first 3 days of an 11-day pair-fed study, the overall weight gain recorded by these animals was normal. Nevertheless, bone growth was inhibited by suspension. Similarly, the total adherent marrow stromal cell population harvested from the femurs and tibias was decreased by tail suspension, and only half the normal number of fibroblastic stromal cell colonies grew when they were cultured. The proliferation of alkaline-phosphatase-positive cells in the stroma was also inhibited. Northern hybridization revealed that the messenger RNA level for transforming growth factor-beta 2 and IGF-II in stromal cell was reduced by tail suspension. The production of IGF-II by marrow stromal cells was also decreased. The steady-state level of five different transcript sizes of IGF-I mRNA was altered differentially by tail suspension. Osteopontin mRNA was also reduced in marrow stromal cells from tail-suspended rats compared with the normal rats. These data suggest that skeletal unloading not only alters the mRNA level for growth factors and peptide production, but also affects the proliferation and osteogenic differentiation of marrow stromal cells. These changes may be responsible for the reduced bone formation in osteopenia and osteoporosis.

Animals↗
PubMed1995

Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina.

The incidence of nutritional rickets in the southern part of Argentina is 8-12 times higher than in the rest of the country. Winter 25(OH)D serum levels in normal population of southern areas are lower than in central and northern areas. To elucidate these differences, we compared the photoconversion of provitamin D3 (7-DHC) to previtamin D3 in two cities: Ushuaia (latitude 55 degrees S) and Buenos Aires (34 degrees S). Ampules containing 7-DHC were exposed to sunlight one day in the middle of each month either from 10:30 a.m. to 2:30 p.m. or from 8:00 a.m. to 5:00 p.m. The percentages of photoproducts formed were determined by high performance liquid chromatography (HPLC). Previous studies have proved that this is a valid model to assess "in vitro" the photoproduction of vitamin D3 in human skin. Previtamin D3 + vitamin D3 formed in Ushuaia were less (p < 0.02) than those found in Buenos Aires during all seasons: summer, (X +/- SEM) 6.4 +/- 0.8% vs. 13.2 +/- 1.8%; autumn, 1.2 +/- 0.7% vs. 6.3 +/- 1.3%; winter, 0.8 +/- 0.7% vs. 3.6 +/- 0.7%; spring, 3.4 +/- 0.5% vs. 9.1 +/- 1.1%. The photoproducts produced from 10:30 a.m. to 2:30 p.m. were similar for each month and latitude to those formed when the ampules were exposed from 8:00 a.m. to 5:00 p.m. We conclude that in Ushuaia there is a prolonged "vitamin D winter" during which cutaneous synthesis of vitamin D is absent, leading to lower serum values of 25(OH)D and contributing to the higher incidence of rickets.

Argentina↗
PubMed1995

Acoustic response properties of single neurons in the central posterior nucleus of the thalamus of the goldfish, Carassius auratus.

Acoustic responses were recorded extracellularly from single neurons in the thalamic central posterior nucleus (CP). Spontaneous activity, best sensitivity, and sharpness of tuning (Q10dB) of CP neurons ranged from 0 to 36 spikes/s, -40 to 5 dB re: 1 dyne/cm2, and 0.18 to 1.80, respectively. The distribution of characteristic frequency (CF) was nonuniform with a mode at 195 Hz. Temporal response patterns of CP neurons (N = 60) were categorized into three groups: phasic (25%), tonic chopper-like (22%), and tonic nonchopper-like (53%) on the basis of peri-stimulus time and inter-spike interval histograms. Most CP neurons (90%) did not phase-lock to tones, and none phase-locked strongly. The properties of CP neurons are similar to those of the midbrain torus semicircularis neurons in spontaneous rates, best sensitivities, nonuniform CF distributions, and in exhibiting level-independent best frequencies. Both CP and toral neurons show a diversity of response patterns resembling those found in the mammalian central auditory system. However, CP neurons have broader tuning and less phase-locking than toral neurons, suggesting different roles in auditory processing. While peripheral frequency analysis is enhanced at the midbrain level, the integration of frequency-selective channels in the thalamus may function in the processing of wideband spectra characteristic of natural sound sources.

Acoustic Stimulation↗
PubMed1995

Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects.

Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorothioate (GEM 91) developed as an anti-human immunodeficiency virus (HIV) agent was carried out in this study. 35S-Labeled GEM 91 was administered to six HIV-infected individuals by means of 2-hour intravenous infusions at a dose of 0.1 mg/kg. Plasma disappearance curves for GEM 91-derived radioactivity could be described by the sum of two exponentials, with half-life values of 0.18 +/- 0.04 and 26.71 +/- 1.67 hours. The radioactivity in plasma was further evaluated by polyacrylamide gel electrophoresis, showing the presence of both intact GEM 91 and lower molecular weight metabolites. Urinary excretion represented the major pathway of elimination, with 49.15% +/- 6.80% of the administered dose excreted within 24 hours and 70.37% +/- 6.72% over 96 hours after dosing. The radioactivity in urine was associated with lower molecular weight metabolites. No drug-related toxicity was observed.

Adult↗
PubMed1995

Population characteristics of hepatic dihydropyrimidine dehydrogenase activity, a key metabolic enzyme in 5-fluorouracil chemotherapy.

Dihydropyrimidine dehydrogenase is the initial rate-limiting enzyme in catabolism of 5-fluorouracil, one of the most widely used cancer chemotherapeutic agents. Previous studies have shown the clinical importance of determination of dihydropyrimidine dehydrogenase in patients with cancer, particularly in those with deficiency of this enzyme who experience severe 5-fluorouracil-associated toxicity (including death) after 5-fluorouracil treatment. In the present study, dihydropyrimidine dehydrogenase activity was determined in 138 donor liver samples. A normal distribution of human liver dihydropyrimidine dehydrogenase activity was shown. The mean enzyme activity was compared across different groups by age, gender, and race, with no significant differences observed except that the mean enzyme activity in women was slightly higher than that observed in men. With use of a polyclonal antibody generated against human liver dihydropyrimidine dehydrogenase, Western blot analysis showed that dihydropyrimidine dehydrogenase protein in the liver cytosol correlated with the activity of this enzyme.

Adult↗
PubMed1995

Expression of thioredoxin random peptide libraries on the Escherichia coli cell surface as functional fusions to flagellin: a system designed for exploring protein-protein interactions.

We have developed a system for probing protein/protein interactions which makes use of the bacterial flagellum to display random peptide libraries on the surface of E. coli. In developing the system the entire coding sequence of E. coli thioredoxin (trxA) was inserted into a dispensable region of the gene for flagellin (fliC), the major structural component of the E. coli flagellum. The resulting fusion protein (FLITRX) was efficiently exported and assembled into partially functional flagella on the bacterial cell surface. A diverse library of random dodecapeptides were displayed in FLITRX on the exterior of E. coli as conformationally constrained insertions into the thioredoxin active-site loop, a location known to be a highly permissive site for the insertion of exogenous peptide sequences into native thioredoxin. To demonstrate that members of this library could be bound and selected via specific protein/protein interactions to a target protein, a method was devised to enable efficient isolation of those bacteria displaying peptides with affinity to immobilized antibodies. We have unambiguously mapped three different antibody epitopes using this method. Peptides selected as FLITRX active-site fusions retain their binding specificity when made as native thioredoxin active-site loop fusions. This will facilitate future structural characterizations and broaden the general utility of the system for exploring other classes of protein-protein interactions.

Amino Acid Sequence↗
PubMed1995

Radiotherapy of ectopic ACTH syndrome due to thoracic carcinoids.

From 1984 to 1990, six patients with histologically and endocrinologically proven ectopic ACTH syndrome were treated in our department. The lesion in five patients was clinically evident, but in the other was occult. All lesions were located within the chest. Four were thymic carcinoid and the other two were bronchial carcinoids. Most of the patients had typical clinical manifestations of Cushing's syndrome. Laboratory tests including histopathological examination confirmed the diagnosis of ectopic ACTH syndrome. The treatment consisted of surgical removal of the mass supplemented by radiotherapy. The results showed that after treatment all patients had satisfactory remission. Two bronchial carcinoid patients have been living for 40 and 88 months respectively without recurrence. Among 4 thymic carcinoid patients, only one has been living with no tumor for 34 months. One patient had recurrence and the other 2 died 32 and 50 months after the treatment respectively. However, the symptoms of two thymic carcinoid patients had not been relieved at all until radiotherapy was given. This paper discusses the method, dose and indications of radiotherapy. It should be pointed out that the prognosis of bronchial carcinoids is good while that of thymic carcinoids is relatively poor.

ACTH Syndrome, Ectopic↗
PubMed1995

[A preliminary study on etiology of atrophic rhinitis in Zunyi].

200 cases (households with atrophic rhinitis (AR) diagnosed from outpatients and mobile medical team as the AR group were studied. Another 200 cases (households) served as the control group, who were residents of countryside and members of a factory in Zunyi, and they have lived in Zunyi for more than 20 years. The subjects between the two groups were similar in age and sex. Each of these two groups was further divided into two groups, the opentype stove group (100 cases) and the closetype stove group (100 cases). The heritability (h2, 59.4 +/- 0.032%) was estimated by using the method of Falconer liability threshold. The concentration of SO2 in living environment was monitored with Parafuchsin colorimetry. The daily average SO2 concentrations have been drawn for comparison. The result showed that the SO2 concentration of living environment in AR group was significantly higher than that in control group (P < 0.01). We believe that the contraction and development of AR were determined by the combination of inheritance with environment. This fact suggests that AR may be transmitted in a multigenic and multifacterial modes.

Adolescent↗
PubMed1995

Carpal tunnel syndrome: etiological, clinical and electrophysiological aspects of 262 cases.

Two hundred and sixty-two patients with carpal tunnel syndrome (CTS) were analyzed retrospectively. Results showed that middle- and older-age women were more apt to have CTS than men, and that the dominant hand was more frequently affected. Hormonal changes, repetitive and forceful movements, awkward positions of hand and wrist, and other factors may be associated with CTS. Typical clinical manifestations include pain and paresthesia in the median nerve territory, worsening at night or in the early morning, and being relieved by shaking the hand. Although the patients may localize the discomfort beyond the territory, sensory changes are variable and not entirely reliable. Conduction abnormalities often appeared selectively in the median nerve distal to the wrist in CTS. If the patient who is clinically suggestive of CTS shows normal conduction with conventional methods, palmar stimulation and inching technique is recommended. The diagnosis of CTS requires confirmation of illness history, symptoms and signs with objective electrodiagnostic tests.

Adult↗
PubMed1995

In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothioate in rats.

The use of antisense oligonucleotides represents a novel, genetically based therapy. The biostability and pharmacokinetics of a 33-mer self-stabilized oligodeoxynucleotide with significant anti-HIV activity was determined in rats after intravenous administration of [35S]oligodeoxynucleotide. Plasma disappearance of the labeled oligodeoxynucleotide could be described by a two-compartment model, with half-lives of 0.54 and 41.44 h. The oligodeoxynucleotide in plasma remained mainly intact. Urinary excretion represented the major elimination pathway, with approximately 27% of the administered dose excreted within 24 h and 57% over 240 h. The majority of radioactivity in urine was attached to degradative products. Fecal excretion was a minor elimination pathway. A wide tissue distribution of the oligonucleotide was observed, with the majority of radioactivity in most tissues being intact. Compared with other linear oligonucleotide phosphorothioates, the self-stabilized oligonucleotide was more stable in vivo, which may be important in development of antisense oligonucleotides as therapeutic agents.

Animals↗
PubMed1995

[Efficacy of praziquantel combined with albendazole in the treatment of clonorchiasis].

This paper reported on the clinical efficacy of praziquantel-albendazole combination in the treatment of clonorchiasis in Guangxi. Two hundred and two cases were divided into three groups. The first group comprised 66 cases who were treated with praziquantel at 180 mg/kg bwt for three days. The second group consisted of 62 cases who were treated with albendazole at 90 mg/kg bwt for three days. In the third group, 74 cases were treated with 90 mg/kg bwt praziquantel plus 45 mg/kg albendazole for three days. The results showed that the negative conversion rates were 98.5%, 61.3% and 87.8% in groups one, two and three, respectively, one month after treatment. In some cases who continued to be egg positive, the reduction rates in faecal egg counts were 99.7%, 65.0% and 97.3%, respectively. Although the cure rate in group three was not as high as in group one, the side effects were more mild and transient and the cost of treatment could be reduced by 60% as compared with group one. In cases with light and moderate infections, the praziquantel-albendazole combination proved more effective. In addition, the praziquantel-albendazole combination was also highly effective for treating those cases who were infected with Ascaris, Trichuris or hookworm.

Albendazole↗
PubMed1995

Effects of caffeine or EDTA post-treatment on EMS mutagenesis in soybean.

Seeds of soybean cultivar LD4 were mutagenically treated with EMS (0.3, 0.5, 0.6, 0.9, 1.5 and 1.8%) for 3 h only or plus caffeine (50 mM) or EDTA (1 mM) post-treatment for 5 h. The experimental results indicated that: (1) of the different concentrations of EMS treatment, the M2 mutation frequency induced with 0.6% EMS was the highest (9.7%). When the EMS concentration was over 0.9%, the mutation frequency decreased rapidly. (2) Of the EMS treatments plus caffeine or EDTA post-treatment, the mutagenic effect of 0.6% EMS was the best for inducing morphological variations. Caffeine post-treatment decreased notably the mutation frequency of EMS treatment; when concentrations of EMS were very high (1.5% and 1.8%), mutation frequencies of EDTA post-treatment were still 5.0% and 4.88%, but no mutants were found in EMS treatment or plus caffeine post-treatment. (3) In the M2 mutation spectrum, 11 kinds of mutant types were observed in EMS treatment or plus caffeine or EDTA post-treatment. Relative frequencies of some mutant types (growth period, plant height, grain size, leaf shape and sterility, etc.) were similar among the three treatments, but EDTA post-treatment could change the relative frequencies of yield characteristics (number of pods and grains, grain weight/plant) induced by EMS treatment only.

Antimutagenic Agents↗