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Biomedical subjects

J Fang

Publications and source records attributed to J Fang.

At least 217 records · Page 12Linked to original sources

[Determination and significance of nitric oxide and tumor necrosis factor-alpha induced by peripheral blood monocyte in vitro in patients with malignant bone tumors].

Peripheral blood monocytes from 15 cases of malignant bone tumors and 12 cases of health volunteers were seperated and induced by lipopolysaccharide(LPS) for 48-hour culture. The supernatant was collected for determining the content of nitrite and tumor necrosis factor-alpha(TNF-alpha) (by Griess and ELISA methods, respectively). The results were as follows: The content of nitrite and TNF-alpha in patients with malignant bone tumors was significantly higher than that in normal control; the content of nitrite and TNF-alpha in the malignant bone tumor group presented the positive correlation (r = 0.8909, P < 0.01). The results suggest that NO and TNF-alpha produced by activated macrophages may be related to the pathogenesis of malignant bone tumors.

Adolescent↗

Lipoprotein (a) concentration and apolipoprotein (a) phenotype in subjects with type 2 diabetes mellitus.

OBJECTIVE: To investigate the apolipoprotein (a) [apo(a)] polymorphism in the patients with type 2 diabetes mellitus and its relationship with complications. METHODS: In this study, we tested apo(a) phenotype via modified Utermann and Guo method in the 40 non-diabetic controls and 176 subjects with type 2 diabetes and analyzed the relationship between apo(a) phenotypes and micro- and macrovascular complications, including nephropathy, neuropathy, retinopathy, hypertension, coronary heart disease and cerebral infarction. RESULTS: Among the 40 non-diabetic controls, the frequencies of S3S2, S4 and S4S2 were 20%, 70% and 10% respectively and the serum lipoprotein (a) [Lp(a)] level was 0.08 +/- 0.07 mg/L. While the frequencies of S2, S3, S3S2, S4, S4S2, S4S3 were 18.18%, 20.45%, 17.05%, 34.09%, 4.55% and 5.68% in the diabetics and the Lp(a) concentration was 0.13 +/- 0.11 mg/L, with significant difference between the diabetics and non-diabetic controls. In comparison with the diabetics without complications, the frequency of apo(a) phenotype significantly differed in patients with nephropathy, nephropathy, hypertension, coronary heart disease and cerebral infarction except for diabetic retinopathy. In comparison with patients with S2 phenotype, the levels of fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG) and glycated hemoglobin A1c (HbA1c) were lower in patients with S4 phenotype. The concentration of Lp(a) and urine albumin index (Alb/Cr) were significantly different among diabetics with different apo(a) phenotype, the highest being in patients with S2, secondly S3, and the lowest S4. CONCLUSION: There were significant differences in the frequency of apo(a) phenotype between subjects with type 2 diabetes and non-diabetic controls, and also in diabetics with or without microvascular and macrovascular diseases. The underlying linkage might be microalbuminuria and insulin resistance.

Adult↗

[Protecting infection by using rhG-CSF in patients with lung cancer during chemotherapeutic courses].

OBJECTIVE: To recognize the prophylactic effect of rhG-CSF used on infection complications secondary to chemotherapy in patients with lung cancer. METHOD: The infection complications and the neutropenia secondary to chemotherapy in 163 cases of lung cancer patients with or without rhG-CSF were retrospectively analyzed. RESULT: Rhg-CSF administration reduced the frequency of infection complications, and there was a significant difference(P < 0.005) in the frequency of infection between the G-CSF group's patients (infections incidence 25%) and non-G-CSF group's (56%). The incidence of neutropenia in G-CSF group' patients is obviously less than that in non-G-CSF group's (P < 0.005). The median number of days of the neutropenia (neutrophil count of < 1.0 x 10(9) in G-CSF group(3 days) is less than that in non-G-CSF group(4 days)(P < 0.001). However, there was no significant difference (P > 0.05) between G-CSF group(63%) and non-G-CSF group(76%) in terms of response of the infection complications. CONCLUSION: Our data has shown that the administration of rhG-CSF as an adjunct to chemotherapy in patients with lung cancer can accelerate neutrophil recovery and shorten the duration of neutropenia, and lead to reductions in the incidence of infection complications, and also has the potential to increase the amount of cytotoxic chemotherapy and the quantity of life.

Adenocarcinoma↗

[Expression of standard and variant CD44 in human lung cancer].

OBJECTIVE: CD44 transmembrane glycoprotein, a cell adhesion molecule, is expressed in most adult tissues and in the majority of neoplasms. Due to alternative splicing, this cell adhesion molecule exists in multiple isoforms, some of which have been associated with specific types of tumors as well as with tumor invasion and metastasis. In this study, we observed the expression of CD44 standard (CD44s) and variant forms (CD44v6) in 96 primary lung carcinomas and 12 cases of metastatic lymph nodes by immunohistochemistry and associated the results with clinical outcome. To understand the correlation of CD44's expression with the histological types, differentiation, progression and metastasis of primary lung carcinomas. METHOD: Formalin-fixed paraffin-embedded archival tissues from 56 squamous cell carcinomas (SCC), 34 adenocarcinomas (ADC), 6 small cell lung carcinomas (SCLC) and 12 metastatic lymph nodes were immunostained after microwave antigen repair with monoclonal antibodies against CD44s and CD44v6, and the results were associated with histological tumor type, tumor stage and metastasis. RESULT: (1) SCC showed much higher membranous expression of CD44s and CD44v6 than ADC (P < 0.01), and there is no expression in all 6 SCLC cases. (2) In 12 metastatic lymph nodes, 10 metastatic lung carcinomas were found strong immunoreactivity for CD44v6 (83%), and in comparison with lung carcinomas without lymph node metastasis (51%), primary lung carcinomas with lymph node metastasis showed strong expression of CD44v6 (91%, chi 2 = 14.92, P < 0.01). (3) The expression of CD44s and CD44v6 is independent from tumor histopathological grading (well, moderate, poor differentiated). Among different tumor stages, however, there is a distinct statistic difference between stage I + II and stage III + IV (chi 2 = 6.05, P < 0.05) with the tendency of higher stage with higher expression of CD44v6. CONCLUSION: CD44 expresses mostly in NSCLC. Moreover, there is an stronger expression of CD44s and v6 in SCC over ADC; Immunopositivity of CD44v6 may suggest a potential of high risk for lymph node metastasis in NSCLC; CD44v6 reactivity may be useful to decide TNM stage of NSCLC, especially to discriminate stage I, II with higher stage.

Adenocarcinoma↗

[Phacoemulsification in myopia and negative or low powered posterior chamber intraocular lens implantation].

OBJECTIVE: The study was designed to investigate the technique and clinical experience of phacoemulsification in myopia and negative or low powered posterior chamber intraocular lens implantation (PC-IOL). METHODS: 120 eyes of 102 cases with myopia and cataract were included (axial length >or=28 mm) and hardness of nucleus was of grade 2 in 5 eyes, grade 3 in 84 eyes, grade 4 in 16 eyes and grade 5 in 15 eyes. Tunnel incision was made and in situ nuclear fracture technique by phacoemulsification was used. Energy and time of emulsification: 50% - 60% of energy was set up and emulsification spent 40s to 2 min. 10 s (mean, 1 min. 11.3s) for nuclear sclerosis of grade 2 or 3.65% - 70% of energy was set up and emulsification spent 48s to 1 min. 22s (mean, 68.7s) for cutting the central nucleus and removing the divided nucleus (grade 4 or 5). RESULTS: There were 120 eyes in this group. Eleven to 22 months after operation (mean 14.5 months) the visual acuities of 0.5 or better with and without correction were obtained in 62.6% and 43.4% respectively. The major complications were corneal edema and rupture of posterior capsule. No retinal detachment and cystoid macular edema were found. CONCLUSION: This operation is suitable for myopia with cataract. It is worth to spread due to good visual result, proper correction of ametropia, prevention of retinal detachment, and decrease of operative complications.

Adult↗

[Cloning and sequencing of the gene coding the sexual stage antigen Pfs48/45 of Plasmodium falciparum].

AIM: To express the antigen Pfs48/45 in vitro and provide an antigen for the development of the transmission-blocking vaccine. METHODS: According to the published nucleotide sequence of Pfs48/45 of Plasmodium falciparum isolate NF54, a pair of oligonucleotides was designed and used as primers(P1, P2). The gene encoding the gametocyte/gamete-specific membrane protein Pfs48/45 of P. falciparum isolate FCC1/HN has been amplified by using polymerase chain reaction (PCR) technique. The PCR product was purified and directly sequenced by the dideoxynucleotide terminator method with 5'-end primer P1. At the same time, the purified PCR product was digested with BamHI and EcoRI and cloned into the plasmid pcDNA3, then the recombinant clones were transformed into E. coli strain TG1. The recombinant plasmid pcDNA3-Pfs48/45 was screened and identified by PCR amplification and restriction analysis. RESULTS: 1. The gene fragment Pfs48/45 was specifically amplified from the genomic DNA of Plasmodium falciparum isolate FCC1/HN; 2. The sequence demonstrated that the that the 5'-end nucleotide and predicted aminoacid sequence of Pfs48/45 from FCC1/HN isolate was basically identical with that from NF54 isolate. We found that the sequence of the Pfs48/45 gene from the isolate FCC1/HN differs from the published sequence(isolate NF54) only at positions 307 and 372(T-->C). The substitution of T-->C at the position of 372 generates a new restriction site Taq I. The PCR product digested by Taq I generates DNA fragment of 984 bp and 379 bp, suggesting that the PCR product is the gene encoding the transmission blocking antigen Pfs48/45; 3. The gene fragment of Pfs48/45 was directly inserted into the BamHI and EcoRI site of plasmid pcDNA3. CONCLUSION: The nucleotide sequence of Pfs48/45 of Plasmodium falciparum isolate FCC1/HN from south China was similar to that of isolate NF54. The recombinant plasmid pcDNA3-Pfs48/45 was successfully constructed, providing a means to evaluate the role and biological function of this sexual-stage-specific protein of Pfs48/45.

Amino Acid Sequence↗

Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources.

The metabolism of the antidepressant drug trazodone to its active metabolite, m-chlorophenylpiperazine (mCPP), was studied in vitro using human liver microsomal preparations and cDNA-expressed human cytochrome P450 (P450) enzymes. The kinetics of mCPP formation from trazodone were determined, and three in vitro experiments were performed to identify the major P450 enzyme involved. Trazodone (100 microM) was incubated with 16 different human liver microsomal preparations characterized for activities of 7 different P450 isoforms. The production of mCPP correlated significantly with activity of cytochrome P4503A4 (CYP3A4) only. Trazodone (100 microM) was then incubated with microsomes from cells expressing human CYP1A1, CYP1A2, CYP2C8, CYP2C9arg, CYP2C9cys, CYP2C19, CYP2D6, or CYP3A4. Only incubations with CYP3A4 resulted in mCPP formation. In the third experiment, the CYP3A4 inhibitor ketoconazole was found to inhibit mCPP formation concentration dependently in both human liver microsomes and in microsomes from cells expressing human CYP3A4. The present results indicate that trazodone is a substrate for CYP3A4, that CYP3A4 is a major isoform involved in the production of mCPP from trazodone, and that there is the possibility of drug-drug interactions with trazodone and other substrates, inducers and/or inhibitors of CYP3A4.

Antidepressive Agents, Second-Generation↗

Mouse latent TGF-beta binding protein-2: molecular cloning and developmental expression.

The molecular cloning and developmental expression of mouse LTBP-2 are presented here. We established the identity of the cDNA by sequence comparison (80% identity with human LTBP-2) and by chromosome localization (mouse chromosome 12, band D, a region of conserved synteny with the human LTBP-2 gene). In contrast to LTBP-1 and LTBP-3, mouse LTBP-2 apparently is a more modular protein, with proline/glycine-rich sequences always alternating with clusters of cysteine-rich structural motifs. We found for the first time that LTBP-2 gene expression in mouse embryos was restricted to cartilage perichondrium and blood vessels, a somewhat surprising result since other LTBP genes are widely expressed in rodent tissues. Therefore, mouse LTBP-2 may play a critical role in the assembly of latent TGF-beta complexes in developing elastic tissues such as cartilage and blood vessel.

3T3 Cells↗

Mice lacking the TNF 55 kDa receptor fail to sleep more after TNFalpha treatment.

Tumor necrosis factor (TNF) is a well characterized sleep-regulatory substance. To study receptor mechanisms for the sleep-promoting effects of TNF, sleep patterns were determined in control and TNF 55 kDa receptor knock-out (TNFR-KO) mice with a B6 x 129 background after intraperitoneal injections of saline or murine TNFalpha. The TNFR-KO mice had significantly less baseline sleep than the controls. TNFalpha dose-dependently increased non-rapid eye movement sleep (NREMS) in the controls but did not influence sleep in TNFR-KO mice. Although TNFR-KO mice failed to respond to TNFalpha, they had an increase in NREMS and a decrease in rapid eye movement sleep after interleukin-1beta treatment. These results indicate that TNFalpha affects sleep via the 55 kDa receptor and provide further evidence that TNFalpha is involved in physiological sleep regulation. Current results also extend the list of species to mice in which TNFalpha and interleukin-1beta are somnogenic.

Animals↗

Influence of nativity on cancer mortality among black New Yorkers.

BACKGROUND: Cancer is the second leading cause of death in U. S., and blacks have higher cancer death rates than whites. The authors conducted an analysis to determine the influence of birthplace on cancer mortality among blacks in New York City. METHODS: Death records for New York City from 1988 through 1992 were linked to the 1990 U. S. Census data. Age-adjusted cancer death rates by race and birthplace were computed. The experience of black residents born in the South and Northeast of the U. S. and in Caribbean countries were compared with that of New York City whites. RESULTS: The cancer mortality rate of blacks exceeded that of whites for males (512.6 vs. 385.6 per 100,000 per year), but was similar for females (270.8 vs. 270.6). However, cancer death rates of Southern-born black males (615.7) were substantially higher than those of black males born in the Northeast (419.1) or the Caribbean (352.4). Carcinomas of the lung, prostate, breast, and colon/rectum accounted for >50% of all cancer deaths. Lung carcinoma mortality varied greatly by birthplace, with Caribbean-born blacks (63.5 and 19.2 for males and females, respectively) having approximately one-third the death rates of Southern-born blacks (187.8 and 52.5 for males and females, respectively), and <50% that of New York City whites (108.7 and 53.2 for males and females, respectively). These differences were present in each age category, but were most pronounced among those age 45-64 years. In striking contrast, death rates from prostate carcinoma were highest in Caribbean-born black men, and this was especially apparent in persons age > or = 65 years. CONCLUSIONS: The generally higher cancer mortality of blacks compared with whites masks even greater intraracial heterogeneity revealed through stratification by birthplace. In general, Caribbean-born blacks are at lower risk of cancer mortality than other blacks, and whites, but their advantage does not hold for prostate carcinoma, for which Caribbean-born men had the highest mortality rate.

Adult↗

Integration of HTLV-1 provirus into mouse transforming growth factor-alpha gene.

Human T cell leukemia virus type 1 (HTLV-1) provirus integration was investigated in mice inoculated with MT-2 cells, a HTLV-1 producing human T-cell line. From spleen DNA derived from a MT-2 cell-injected mouse, we cloned a HTLV-1 integration site by ligation-mediated PCR. The nucleotide sequence showed that HTLV-1 provirus was integrated into an intron of the mouse transforming growth factor-alpha gene in the reverse orientation. This result provides for the first time molecular evidence that mice can be infected with HTLV-1.

Amino Acid Sequence↗

A mutation in E. coli SSB protein (W54S) alters intra-tetramer negative cooperativity and inter-tetramer positive cooperativity for single-stranded DNA binding.

E. coli SSB tetramer binds with high affinity and cooperatively to single-stranded (ss) DNA and functions in replication, recombination and repair. Curth et al. (Biochemistry, 32 (1993) 2585-2591) have shown that a mutant SSB protein, in which Trp-54 has been replaced by Ser (W54S) in each subunit, binds preferentially to ss-polynucleotides in the (SSB)35 mode in which only 35 nucleotides are occluded per tetramer under conditions in which wild-type (wt) SSB binds in its (SSB)65 mode. The W54S mutant also displays increased UV sensitivity and slow growth phenotypes, suggesting defects in vivo in both repair and replication (Carlini et al. (Molecular Microbiology, 10 (1993) 1067)). We have characterized the energetics of SSBW54S binding to poly(dT) as well as short oligodeoxyribonucleotides (dA(pA)69, dT(pT)34, dC(pC)34) to determine the basis for this dramatic change in binding mode preference. We find that the W54S mutant remains a stable tetramer; however, its affinity for ss-DNA as well as both the intra-tetramer negative cooperativity and its inter-tetramer positive cooperativity in the (SSB)35 mode (omega 35) are altered significantly compared to wtSSB. The increased intra-tetramer negative cooperativity makes it more difficult for ss-DNA to bind the third and fourth subunits of the W54S tetramer, explaining the increased stability of the (SSB)35 mode in complexes with poly(dT). When bound to dA(pA)69 in the (SSB)35 mode, W54S tetramer also displays a dramatically lower inter-tetramer positive cooperativity (omega 35 = 77(+/-20)) than wtSSB (omega 35 > or = 10(5)) as well as a significantly lower affinity for ss-DNA. These results indicate that a single amino acid change can dramatically influence the ability of SSB tetramers to bind in the different SSB binding modes. The altered ss-DNA properties of the W54S SSB mutant are probably responsible for the observed defects in replication and repair and support the proposal that the different SSB binding modes may function selectively in replication, recombination and/or repair.

Biopolymers↗

Genes coding for mouse activin beta C and beta E are closely linked and exhibit a liver-specific expression pattern in adult tissues.

Five activin beta subunits have been isolated to date, and a comparative analysis of amino acid identity has suggested that the activin beta C, beta D and beta E subunits represent a distinct subset. Based on genomic cloning studies, we now report that the mouse activin beta C and beta E genetic loci are closely linked-i.e, the coding sequences are separated by 5.5-kbp. These genes also show similarities in structural organization as well as a unique liver-restricted pattern of expression in adult mice. Our results suggest that tandem duplication of an ancestral gene generated the mouse activin beta C and beta E genetic loci, and they provide further evidence for the postulate that the beta C-beta E subunits form a distinct subset of related activins. To our knowledge, this report is the first to demonstrate close chromosomal linkage between members of the TGF-beta superfamily as well as a liver-restricted expression pattern for a TGF-beta-like gene.

Activins↗

Study of single motor unit discharge patterns using 1/f process model.

We developed a technique to study temporal discharge patterns of single motor units using 1/f process model, whose fractional parameter gamma was shown to be a useful indicator for distinguishing between discharge behaviors of single motor units of normal subjects and patients with upper motor neuron lesions. We have studied a total of 47 motor units in 3 normal subjects, and 41 in 3 patients with upper motor neuron lesions from biceps and extensor digitorum communis muscles during steady contraction. The parameter gamma was estimated with an algorithm based on wavelet analysis. The mean value of gamma in patients was 1.52, and the mean value of gamma in normal subjects was -0.06. These results suggest that 1/f process can be used to document the impaired motor control mechanisms at single motor unit level.

Arm↗

Motor unit number estimation by spatial-temporal summation of single motor unit potentials.

Current techniques for motor unit number estimation (MUNE) rely on the amplitude of the compound muscle action potential (CMAP) evoked by supramaximal stimulation and mean amplitude of single motor unit potentials (SMUPs). The phase cancellation during summation is not considered. We developed a technique to address this issue. Slow and fast types of motor unit potentials were collected from 5 normal subjects from their abductor pollicis brevis muscles by low-level voluntary contractions, and near-threshold nerve stimulation, respectively. Two of each type of SMUPs were used as templates for reconstructing the best fitted CMAP using a feed-forward neural network. The total number of SMUPs simulated from the four templates during the reconstruction served as MUNE. The mean MUNE was 222 +/- 98. The technique is simple and noninvasive, and may be applied in the future for MUNE in patients.

Action Potentials↗

Atypical acinar cell foci in human pancreas. Morphological and morphometric analysis.

CONCLUSION: The morphological and quantitative findings of the present study suggest that atypical acinar cell foci are not neoplastic in nature. BACKGROUND: Atypical acinar cell foci (AACF) are rare and unusual lesions in the human pancreas. The biological nature of AACF is poorly understood, and is not clear whether they represent neoplastic or degenerative changes in the acinar cells. METHODS: To further characterize and understand the significance of AACF in relation to acinar cell tumor development, we have examined these lesions by light and electron microscopy and evaluated the growth pattern by measuring cell proliferation and the size of the foci in the pancreas of a 16-yr-old male. RESULTS: The pancreas was grossly unremarkable. AACF were randomly distributed throughout the pancreas, well delineated, and showed minimal variation in sizes. The constituent cells contained uniform nuclei, pale vacuolated cytoplasm, and exhibited low nuclear-cytoplasmic ratio. Electron microscopic examination showed a few zymogen granules and markedly dilated rough endoplasmic reticulum. Proliferative index in AACF (13%) was less than in adjacent uninvolved acinar tissue (19%). Quantitative stereological analysis showed the pancreas to contain approximately 1800 AACF/cm3 with a mean focal diameter of 360 microns.

Adolescent↗

Chondrogenic cell differentiation from membrane bone periostea.

Most craniofacial membrane bones are derived from neural crest (NC) cells. Interaction between NC cells and epithelium, and cellular condensation, are two major events that lead NC cells to become osteoblasts that deposit membrane bone. Unlike endochondral bone, membrane bone formation is not preceded by cartilage formation in normal development. However, chondrogenic potential in membrane bone is evidenced by several cartilage-associated phenomena in vivo. Furthermore, in vitro, periosteal cells of some membrane bones express cartilage phenotype gene products and even differentiate into chondrocytes. Hence, membrane bone periosteal cells can undergo chondrogenic differentiation. The precursor of chondrogenic cells in membrane bone is not clear: chondrocytes were proposed to arise from unipotential chondroprogenitor cells, bi- or multipotential progenitor cells, or differentiated osteogenic cells. There is experimental support for each, but studies on clonal and cell cultures provided more support for a common precursor of both chondro- and osteogenic cells. Moreover, in periostea, chondrogenesis probably arises from a differentiated cell type. Membrane bone formation in periostea may include a transient cell stage that is able to undergo both osteo- and chondrogenesis. Osteogenesis would be the normal pathway, but chondrogenesis can be evoked in certain microenvironments. It is not known whether microenvironmental factors trigger chondrogenesis through a universal molecular mechanism, nor is the molecule that triggers chondrogenesis known. Expression of neural cell adhesion molecule (NCAM) is down-regulated during commitment of periostal cells for secondary chondrogenesis, suggesting a possible regulatory role for NCAM in the alternative differentiation pathways of periosteal cells.

Animals↗