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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 613 records · Page 34Linked to original sources

Finite element modelling of a residual lower-limb in a prosthetic socket: a survey of the development in the first decade.

A review is presented of the existing finite element models developed from 1987 to 1996 for the biomechanics of lower-limb prostheses. Finite element analysis can be a useful tool in investigating the mechanical interaction between the residual limb and its prosthetic socket, and in computer-aided design and computer-aided manufacturing of prosthetic sockets. Various assumptions and simplifications are made in these models to simplify the actual problem with complex geometry, material properties, boundary and interfacial conditions, as well as loading situations. The analyses can provide the information on the stress distribution at the stump/socket interface and within the residual limb tissues. More recently, nonlinear models have been developed taking into consideration the process of socket rectifications, the slip/friction conditions and material large deformation. The models so far developed have provided some basic understanding of the biomechanics. Comparison of the predictions of these models with experimental measurements indicated that the predicted stresses were within the ranges measured, although one-to-one correspondence was difficult to achieve. Further research is still required in order to improve these models to obtain higher precision in the results taking into account nonlinear and dynamic effects.

Artificial Limbs↗

Two new diterpene glycosides from the soft coral lemnalia bournei

Two new bicyclic diterpene glycosides, lemnaboursides B and C (1, 2), have been isolated from the Chinese soft coral Lemnalia bournei. They are the monoacetate derivatives of lemnabourside (3) previously obtained from the same species. The structures of compounds 1 and 2, which showed weak cytotoxicity against HepA, S180A and EAC cells, respectively, were established from spectral data and chemical transformations.

Journal Article↗

Pharmacological characterization of an endogenous negative inotrophic factor (ENIF) from porcine heart.

Recently we have been successful in isolating an endogenous negative inotropic factor (ENIF) from porcine left ventricular tissue. In this study, we have characterized its pharmacological properties. The results of the study demonstrated that ENIF produces a concentration-dependent negative inotropic response on both guinea pig left atria and right ventricular trabeculae. The maximal reduction in contractile force produced by 300 ul of ENIF (5 ml bath) on atria and trabeculae were 90.0 +/- 0.8% and 77.5 +/- 6%. Atria, however, was significantly more sensitive to ENIF than trabeculae. The ED 50 of ENIF for atria was found to be 38 ul as opposed to ED 50 of 100 ul of ENIF for trabeculae. Acetylcholine (ACh), a muscarinic receptor agonist, decreased the contractile force of guinea pig atria in a dose-dependent manner with a maximal decline in the contractile force of 90%. However, none of the concentration of ACh used affected the contractile function of the trabeculae. Atropine (1 uM) completely blocked the negative inotropic response on atria of all the doses of ACh used. The same dose of atropine, however, was unable to influence the negative inotropic effect of any of the doses of ENIF used on either the atria or trabeculae preparations in our study. The maximal decline in the contractile force of atria was e.g. 94 and 95% in the presence and absence of atropine respectively. These data demonstrate that the myocardial negative inotropic effect of ENIF is not mediated via the cholinegic receptor mechanism.

Acetylcholine↗

Efficiency and efficacy of the electrogastrogram.

The efficiency and efficacy of the electrogastrogram (EGG) involve a few practical factors, including recording length, sample size, and the characteristics of subjects. The aim of this study was to investigate the effect of these factors on the accuracy of EGG analysis. Gastric myoelectrical activity was recorded using electrogastrography in 24 subjects (ages 22-91 years) for 1 hr in the fasting state and 2 hr after a test meal. Computerized spectral analysis was performed to compute EGG parameters, including dominant frequency, dominant power, and the percentage of 2-4 cycles per minute (cpm) slow waves. A parameter called misinterpretation was defined to investigate the effect of recording length. The results were as follows: (1) Using the recording length of 1 hr in each state as a gold standard, the misinterpretation for the recording length of 30 min was 27% for the dominant frequency and 17% for the dominant power. When the recording length was reduced to 15 min, the misinterpretation increased to 61% for the dominant frequency and 38% for the dominant power. (2) With a sample size of 10 subjects and a recording length of 60 min, a statistically significant postprandial increase was observed in the dominant frequency and power, and a trend in the postprandial increase of the regularity of the EGG was noted. When the sample size increased to 24 subjects, a significant postprandial increase was found in all these parameters. (3) None of the EGG parameters exhibited any significant difference between the younger and older subjects or between men and women. In conclusion, a recording length of 30-60 min seems to be appropriate and produces reliable and predictable results. Age and gender do not affect any of the EGG parameters.

Adult↗

Gastric myoelectrical activity in healthy children and children with functional dyspepsia.

The aim of this study was to investigate abnormalities in pediatric patients with functional dyspepsia. Fifteen symptomatic pediatric patients diagnosed with functional dyspepsia and 17 aged-matched healthy controls were studied. Gastric myoelectrical activity was recorded using surface electrogastrography for 1 hr in the fasting state and 1 hr after a test meal. It was found that, in comparison with the controls, the children with functional dyspepsia had a lower percentage of 2- to 4-cpm slow waves in both fasting state (66.0+/-4.7% vs 79.7+/-3.1%, P < 0.07) and fed state (72.4+/-5.4% vs 85.0+/-2.9%, P < 0.04), and a significantly higher instability of the dominant frequency in both fasting state (0.50+/-0.05 vs 0.31+/-0.04, P < 0.01) and fed state (0.39+/-0.05 vs 0.25+/-0.03, P < 0.05). It was also found the postprandial increase in EGG dominant power in the patients was inversely correlated with the total symptom score (r = 0.63, P = 0.03). It was concluded that abnormal gastric myoelectrical activity may play a role in the pathogenesis of pediatric functional dyspepsia.

Adolescent↗

A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability.

The retinoblastoma (RB) gene is one of the most extensively studied tumour-suppressor genes. Deletion or inactivation of both RB alleles is an essential, rate-limiting step in the formation of retinoblastoma and osteosarcoma that arise in families that carry mutant RB (ref. 2). RB inactivation is also found in other human tumours. Whereas loss of RB function is associated with the loss of cellular proliferative control, introduction of a wild-type RB can suppress cell growth and tumorigenicity. Thus, identification of factors that interfere with and/or control the function of the RB protein is critical for understanding both cell-cycle control and oncogenesis. Here we describe a new gene, Bog (for B5T over-expressed gene), which was identified and shown to be overexpressed in several transformed rat liver epithelial (RLE) cell lines resistant to the growth-inhibitory effect of TGF-beta1, as well as in primary human liver tumours. The Bog protein shares homology with other retinoblastoma-binding proteins and contains the Rb-binding motif LXCXE. Using the yeast two-hybrid system and co-immunoprecipitation, we demonstrated that Bog binds to Rb. In vivo, Bog/Rb complexes do not contain E2F-1, and Bog can displace E2F-1 from E2F-1/Rb complexes in vitro. Overexpression of Bog in normal RLE cells conferred resistance to the growth-inhibitory effect of TGF-beta1. Furthermore, normal RLE cells are rapidly transformed when Bog is continuously overexpressed and form hepatoblastoma-like tumours when transplanted into nude mice. These data suggest that Bog may be important in the transformation process, in part due to its capacity to confer resistance to the growth-inhibitory effects of TGF-beta1 through interaction with Rb and the subsequent displacement of E2F-1.

Amino Acid Sequence↗

Solution structure of a protein inhibitor of neuronal nitric oxide synthase.

The structure of the neuronal nitric oxide synthase inhibitory protein, PIN (protein inhibitor of nNOS), has been determined by NMR spectroscopy. Two N-terminal antiparallel alpha-helices pack against a four-stranded antiparallel beta-sheet in the C-terminal region of the protein, forming a two-layer alpha/beta plait. The three dimensional structure of PIN resembles the fold of the B-chain of aspartylglucosaminidase. A non-prolyl cis peptide bond was found between Pro 52 and Thr 53 of the protein. PIN has a large solvent-exposed hydrophobic surface that contains a cavity and is rimmed with positive charges. This surface may serve as the primary target-binding region for this multi-functional regulatory protein.

Amino Acid Sequence↗

Isolation of 24 novel cDNA fragments from microdissected human chromosome band.

The strategy of isolating the band-specific expression fragments from a probe pool generated by human chromosome microdissection was reported. A chromosome 14q24.3 band-specific single copy DNA pool was constructed based on this probe pool. Using total DNA of the pool as probe to hybridize the human marrow cDNA library, 68 primary positive clones were selected from 5 x 10(5) cDNA clones. Among these primary clones, 32 secondary clones were obtained after second-round screening and designed as cFD14-1-32. Finally, 24 band-specific expression fragments were identified from these 32 positive clones by DNA hybridization. Those band-specific clones can hybridize to both 14q24.3 DNA and human genomic DNA but can't hybridize to 17q11-12 DNA. Partial sequences of 13 fragments of them were sequenced and identified as novel cDNA sequences, and these sequences were proved to have some homology with known genes in NCBI database. Analysis of expression spectrum of cFD14-1 suggested that the cDNA fragments thus obtained should be used to isolate the genes can not been cloned in 14q24.3 region.

Blotting, Northern↗

Granulocyte-macrophage colony-stimulating factor induces the differentiation of murine erythroleukaemia cells into dendritic cells.

Dendritic cells (DC) are professional antigen-presenting cells (APC) within the immune system and antigen-pulsed DC can be used as an effective vaccine for active immunotherapy of cancer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the generation of DC. We previously showed that GM-CSF can induce murine erythroleukaemia cells (FBL-3) to differentiate into monocyte-like cells. To develop a new vaccinating method to stimulate the host immune response to leukaemia, we further investigate whether FBL-3 cells induced by GM-CSF can differentiate into DC in the present study. After being treated with GM-CSF, FBL-3 cells expressed high levels of 33D1 and NLDC-145, which are the specific markers of DC. The expression of MHC-II, B7-1, B7-2 and vascular cell adhesion molecule-1 (VCAM-1) was up-regulated markedly; the typical morphology of DC were also observed by electron microscopy. Functionally, the GM-CSF-induced FBL-3 cells could apparently stimulate the proliferation of naive allogeneic and autologous T lymphocytes and induce the generation of specific CTL more efficiently than the wild-type FBL-3 cells. Mice immunized with GM-CSF-induced FBL-3 cells could resist the subsequent challenge with the wild-type FBL-3 cells. Collectively, these data indicate that GM-CSF differentiates murine erythroleukaemia cells into DC phenotypically, morphologically and functionally. FBL-3-derived DC can be used as a new type of vaccine. Our results may have important implications for the immunotherapy of leukaemia.

Adoptive Transfer↗

Effects of amidinopiperidine-4-carboxylic acid 4-tert-butylphenyl ester, a specific trypsin inhibitor, on the growth of HL-60 cells.

Previous results showed that the synthetic compound amidinopiperidine-4-carboxylic acid 4-tert-butylphenyl ester (APCA-OPhBut), a trypsin inhibitor, could specifically inhibit the activity of proteinase In and lead to growth arrest of Hela cells in early S phase. In this study, APCA-OPhBut exhibited inhibitory effects on the growth of HL-60 cells. Apoptotic cells were observed when the cells were cultured with APCA-OPhBut above 50 microM. Time course studies demonstrated that apoptotic cells were increased in a dose- and time-dependent manner. Flowcytometric assays demonstrated that HL-60 cells underwent slight G1 growth arrest after treatment with APCA-OPhBut. No change of Bcl-2 protein level was detected. The findings suggest that the intracellular trypsin-like protease inhibited by APCA-OPhBut not only plays a key role in DNA synthesis initiation but is also necessary for survival of certain cell lines.

Apoptosis↗

Role of tyrosine phosphorylation in ligand-induced regulation of transcytosis of the polymeric Ig receptor.

The polymeric Ig receptor (pIgR) transcytoses its ligand, dimeric IgA (dIgA), from the basolateral to the apical surface of epithelial cells. Although the pIgR is constitutively transcytosed in the absence of ligand, binding of dIgA stimulates transcytosis of the pIgR. We recently reported that dIgA binding to the pIgR induces translocation of protein kinase C, production of inositol triphosphate, and elevation of intracellular free calcium. We now report that dIgA binding causes rapid, transient tyrosine phosphorylation of several proteins, including phosphatidyl inositol-specific phospholipase C-gammal. Protein tyrosine kinase inhibitors or deletion of the last 30 amino acids of pIgR cytoplasmic tail prevents IgA-stimulated protein tyrosine kinase activation, tyrosine phosphorylation of phospholipase C-gammal, production of inositol triphosphate, and the stimulation of transcytosis by dIgA. Analysis of pIgR deletion mutants reveals that the same discrete portion of the cytoplasmic domain, residues 727-736 (but not the Tyr734), controls both the ability of pIgR to cause dIgA-induced tyrosine phosphorylation of the phospholipase C-gammal and to undergo dIgA-stimulated transcytosis. In addition, dIgA transcytosis can be strongly stimulated by mimicking phospholipase C-gammal activation. In combination with our previous results, we conclude that the protein tyrosine kinase(s) and phospholipase C-gammal that are activated upon dIgA binding to the pIgR control dIgA-stimulated pIgR transcytosis.

Animals↗

Escherichia coli prlC gene encodes a trypsin-like proteinase regulating the cell cycle.

Proteinase In has previously been described as displaying a trypsin-like proteinase activity that momentarily appears immediately before DNA synthesis in the cell cycle of Escherichia coli synchronized by phosphate starvation and which is closely related to the initiation of DNA replication [Kato, M., Irisawa, T., Ohtani, M., and Muramatu, M. (1992) Eur. J. Biochem. 210, 1007-1014]. We purified the proteinase In from E. coli C600 and found that the 15 amino acid residues of its amino-terminal were identical with those of oligopeptidase A (OpdA), the product of the E. coli prlC gene. The purified proteinase had a molecular mass of approximately 67 kDa, which was also the same as that of oligopeptidase A. To further elucidate the relationship between proteinase In and oligopeptidase A, we assembled an expression vector to direct the synthesis of E. coli oligopeptidase A. The protein was expressed at a high level in E. coli BL21(DE3) and was produced mostly in the soluble, active form. Both the recombinant enzyme (rPrlC) and the purified proteinase In could hydrolyze trypsin substrates for proteinase In as well as benzyloxycarbonyl Ala- Ala-Leu p-nitroanilide (Z-AALpNA), described as a synthetic substrate for oligopeptidase A. The effects of various protease inhibitors on rPrlC were also very similar to those on proteinase In. The trypsin inhibitors 4-guanidino benzoic acid 4-tert-butylphenyl ester and antipain strongly inhibited the trypsin-like proteinase activity of the recombinant enzyme, but had no effect on its Z-AALpNA hydrolyzing activity. Cobalt ion, which greatly enhanced the OpdA activity, slightly inhibited the trypsin-like activity of the recombinant enzyme. These results strongly suggest that proteinase In is encoded by the E. coli prlC gene and is a multi-functional proteinase with two separate active sites.

Base Sequence↗

Update on the infratemporal fossa approaches to nasopharyngeal angiofibroma.

OBJECTIVES: Review of preoperative evaluation, surgical management, and outcome of patients operated on for nasopharyngeal angiofibroma using lateral infratemporal fossa approaches. STUDY DESIGN: Retrospective review of 20 patients with either extensive (Fisch class IIIa to IVb, n = 17) or less massive (Fisch class II, n = 3) nasopharyngeal angiofibromas. Analysis of preoperative radiologic classification and angiography and description of indications and surgical techniques of the infratemporal fossa approaches types C and D. Evaluation of the surgical morbidity and radicality of tumor removal. METHODS: Clinical data were obtained from medical records from 1987 to 1994. Tumor classification, preoperative symptoms, type of surgery, and neuroradiologic and surgical complications were evaluated. The completeness of tumor removal was assessed using postoperative magnetic resonance imaging. RESULTS: Temporary visual disturbance or headache, or both, was seen in two of 20 patients after superselective tumor embolization, and further visual diminution was observed in one of six patients after balloon occlusion of the internal carotid artery. Radical resection was obtained in 80% of the cases. The infratemporal fossa type C approach was used in 16 of the cases, with type D approaches used in the other four. There were no deaths. The major morbidity was the conductive hearing loss associated with the type C approach. CONCLUSIONS: Preoperative embolization (and balloon occlusion in selected cases) remains an important adjunct with minimal morbidity. The lateral infratemporal fossa approaches yield a high rate of radical tumor removal (80%) and a low rate of recurrence (6%). If applicable, the type D approach avoids the conductive hearing loss but allows direct tumor access into the infratemporal and pterygopalatine fossae.

Adult↗

A joint choice model of the decision to seek depression treatment and choice of provider sector.

OBJECTIVES: Using a community-based sample of currently depressed subjects, this research modeled the joint decision to seek depression treatment and choice of provider sector (primary care or specialty mental health). The objective was to identify those subject-specific case-mix factors and those provider sector-specific access measures that significantly impacted this joint decision. METHODS: A community-based sample of 435 Arkansans with current depression symptoms was compiled using random digit dialing and the Burnam depression screener. Study subjects were administered baseline and 6-month follow-up surveys. All medical, pharmaceutical, and insurance records were collected and abstracted to verify service use and depression treatment. Three discrete choice model specifications were tested: sequential binary logit models, a multinomial logit model, and a nested logit model. The nested logit model makes less restrictive assumptions about the patterns of substitution across treatment alternatives than the other model specifications. RESULTS: In the 6 months after baseline, 73.3% of the sample did not seek depression treatment, 18.9% sought care from a primary care provider, and 7.8% sought care from a mental health specialist. A likelihood ratio test identified the nested logit model as the preferred model specification (chi 2 < or = 0.05), indicating that the expected maximum utility of sector choice significantly affects the decision to seek treatment. Provider sector-specific access measures (e.g., insurance coverage and availability) significantly impacted sector choice and, thus, the decision to seek treatment. Subject-specific case-mix factors (e.g., age, gender, employment status, depression severity, and psychiatric comorbidity) significantly affected the decision to seek treatment. CONCLUSIONS: Sector-specific access measures significantly impact both provider sector choice and the decision to seek treatment. Because the primary care and specialty care treatment alternatives were more substitutable with one another than with the no treatment option, changes in access affected sector choice more than the decision to seek treatment.

Adult↗

Rural-urban differences in depression treatment and suicidality.

OBJECTIVES: Because there are fewer per capita providers trained to deliver mental health services in rural areas, the authors hypothesized that depressed rural individuals would receive less outpatient treatment and report higher rates of hospital admittance and suicide attempts than their urban counterparts. METHODS: The authors recruited 74% of eligible participants (n = 470) from a 1992 telephone survey and followed up 95% of subjects for 1 year. The authors collected data from subjects on psychiatric problems and service use and from insurers/providers on treatment and expenditures. RESULTS: Although there were no rural-urban differences in the rate, type, or quality of outpatient depression treatment, rural subjects made significantly fewer specialty care visits for depression. Depressed rural individuals had 3.05 times the odds of being admitted to the hospital for physical problems (P = 0.02) and 3.06 times the odds of being admitted for mental health problems (P = 0.08) during the year. Elevated rates of hospital admittance disappear in models controlling for number of specialty care depression visits in the previous month. Rural subjects reported significantly more suicide attempts during the period of 1 year (P = 0.05). CONCLUSIONS: Additional work is warranted to determine how to alter barriers to outpatient specialty care if the rural health care delivery system is to provide cost-effective depression care.

Adolescent↗

A radioiodinated biocytin derivative for in-vivo applications.

Radioiodinated biocytin derivatives are potentially useful for multi-step tumour targeting using the avidin-biotin system. We synthesized a radioiodinated biocytin derivative and evaluated its properties in vivo. We labelled biocytin with 125I by coupling biocytin to radioiodinated N-succinimidyl 3-(tri-n-butyl-stannyl) benzoate, and assessed its binding to avidin and its biodistribution in normal and tumour-bearing mice. When the synthesized biocytin was incubated with immobilized avidin, more than 94% of the radioactivity was bound. However, after 2 h incubation in serum, only 40% of the radioactivity was bound to the avidin. The iodinated biocytin derivative was characteristically taken up by the liver and the kidneys when injected intravenously into mice. In mice bearing an intraperitoneal tumour xeno-graft, 125I-biocytin and 111In-biotin were co-injected intraperitoneally 4 h after the intraperitoneal administration of avidin, which accumulated in the intraperitoneal tumours. At 2 and 24 h, the tumour uptake of 125I-biocytin was 8.2 and 3.8% ID/g respectively, whereas that of 111In-biotin was 20.0 and 18.7% ID/g respectively. When radioiodinated, biocytin retains its binding capacity to avidin, and it localizes well with high tumour-to-normal tissue ratios early post-injection using the two-step method, but compared to 111In-biotin it is unstable. We conclude that the stability of the product in serum needs to be improved prior to in-vivo applications.

Animals↗

Effect of radiation and tirapazamine (SR-4233) on three melanoma cell lines.

In this study the response of three melanoma cell lines to single doses of radiation, to the bioreductive drug tirapazamine (SR-4233) and to the combination of radiation and tirapazamine was determined. Tirapazamine is a bioreductive drug with specific cytotoxicity in hypoxic conditions. Three melanoma cell lines (MM576, MM96L and murine B16-F10) were exposed to increasing concentrations of tirapazamine to assess cytotoxicity under aerobic and hypoxic conditions. Also, clonogenic survival after single doses of 4 MV X-rays was determined under aerobic and hypoxic conditions, with and without 20 microM tirapazamine. Tirapazamine was an effective hypoxic cytotoxin in the three cell lines. The concentrations of tirapazamine causing equal cell kill were 1000 mM for aerobic cells and 50 mM for hypoxic cells. The oxygen enhancement ratios for single X-ray doses were between 2 and 3 for all the cell lines. Addition of 20 microM tirapazamine to hypoxic cells 1 h before irradiation produced the same radiosensitivity as aerobic cells. Tirapazamine had a minimal effect on the radiosensitivity of aerobic cells. Since melanomas are known to contain hypoxic cells which may reduce their radiosensitivity, these in vitro results have demonstrated the potential of tirapazamine to overcome the radioresistance of hypoxia and give encouragement for further studies.

Animals↗

A common position-dependent mechanism controls cell-type patterning and GLABRA2 regulation in the root and hypocotyl epidermis of Arabidopsis.

A position-dependent pattern of epidermal cell types is produced during root development in Arabidopsis thaliana. This pattern is reflected in the expression pattern of GLABRA2 (GL2), a homeobox gene that regulates cell differentiation in the root epidermis. GL2 promoter::GUS fusions were used to show that the TTG gene, a regulator of root epidermis development, is necessary for maximal GL2 activity but is not required for the pattern of GL2 expression. Furthermore, GL2-promoter activity is influenced by expression of the myc-like maize R gene (35S::R) in Arabidopsis but is not affected by gl2 mutations. A position-dependent pattern of cell differentiation and GL2-promoter activity was also discovered in the hypocotyl epidermis that was analogous to the pattern in the root. Non-GL2-expressing cell files in the hypocotyl epidermis located outside anticlinal cortical cell walls exhibit reduced cell length and form stomata. Like the root, the hypocotyl GL2 activity was shown to be influenced by ttg and 35S::R but not by gl2. The parallel pattern of cell differentiation in the root and hypocotyl indicates that TTG and GL2 participate in a common position-dependent mechanism to control cell-type patterning throughout the apical-basal axis of the Arabidopsis seedling.

Arabidopsis↗