Colonic pressure data processing based on independent component analysis.

The Colonic manometry is an important technique to evaluate human colonic motor functions, which are critical for doctors to understand the pathology of intestinal diseases like slow transit constipation (STC) and colonic inertia (CI). However, in the obtained pressure signals, several patterns of colonic motor activities as well as noises mixed together, which made it difficult to observe the information people really needed. In this article, a new method was proposed to extract patterns of colonic motility from the mixed signals, so that researchers could study them thoroughly. Colonic pressure recordings from 26 volunteers were obtained by the water-perfused manometry catheters. Then independent component analysis (ICA) was introduced, which successfully separated colonic motility patterns and noises into four independent components. And according to the rhythm of contractions examined by ICA, subjects' colonic motility could be divided into three types: regular rhythm (12 subjects), slow rhythm (8 subjects) and disordered (6 subjects), which exactly accorded with their original diagnosis.

A stable wireless energy transmission system for gastrointestinal microsystems.

A wireless energy transmission system using a Helmholtz primary coil outside and a 3-dimensional secondary coil inside the body is introduced. It is designed to transmit stable power to a gastrointestinal microsystem regardless of its position and orientation when working in the gastric tract. Up to 310 mW of usable DC power can be delivered under worst-case geometrical conditions. Measured data of the system performance are presented and evaluated.

Non-invasive method to detect and locate haemorrhagic focus of GI tract.

Traditional diagnostic methods do not work well for gastrointestinal bleeding, and location of the haemorrhagic focus is even more difficult. Here a novel method with a microelectronic system is presented effectively to detect and locate the haemorrhagic focus. The outstanding advantage of this method is that it is non-invasive. The composition and working principles of the system are described in detail. Key to this system is the development of a haemoglobin (Hb) sensor. Through MEMS technology a micro haemoglobin sensor is developed and fabricated. The sensor's response performance, pH dependence and temperature dependence are tested experimentally. Initial tests suggest that the device is sufficiently sensitive to Hb concentration and insensitive to pH and temperature changes in the working range. As a result, the system has potential for development of an advanced instrument for detecting, localizing and treating gastrointestinal bleeding.

Simultaneous assessment of the intraluminal pressure and transit time of the colon using a telemetry technique.

Colonic motility disorders are common conditions. However, our understanding of normal and pathological motor functions of the colon remains limited, mainly due to the technical difficulties in accessing this organ for study. To investigate colonic motility under normal physiological conditions, we have developed a novel monitoring system based on a telemetry technique. The system is capable of prolonged and noninvasive measurement of intraluminal pressure changes and transit time of intra-colonic contents. To test the in vivo performance of the monitoring system, 15 healthy volunteers and 15 patients with functional constipation (FC) participated in this study. A single-use telemetry capsule embedded with sensors was ingested by the subjects. The capsule is capable of transmitting colonic pressure and temperature wirelessly. The time of the telemetry capsule entering the segmental colon was detected by ultrasonic detection of the batteries in capsule. Pressure recordings confirmed in general a circadian behavior of colonic motility, as well as its response to waking and meals. In the FC patients, the contractile response to morning awakening and meal ingestion was significantly lower compared to the controls. The transit time measured using this method agreed with the time calculated from radiopaque markers (r = 0.89, p < 0.05). The clinical study proved both the reliability and the noninvasiveness of the system. This capsule-style manometric system may represent a useful tool for the study of physiology and pathology of colonic motor disorders.

An earthworm-like microrobot for colonoscopy.

Miniature robotics for colonoscopy has become a hot research topic with the development of minimally invasive surgery (MIS). In this paper, a novel microrobot for colonoscopy that operates based on a simulation of the squirming motion of the earthworm is described. The robot uses a unique driving unit called a linear electromagnetic driver. The prototype measures 9.5 mm in diameter and 120 mm in length. It is driven by a linear direct current (DC) motor designed and manufactured by the authors. This paper describes the prototype, locomotion principle, and control system in detail. It then describes two models that were built to study the robot's ability to move in the viscoelastic colon environment. A slepe model of motion was developed and some mathematical evaluations of locomotion conditions were conducted. Experiments to test the creeping ability of the prototype on a slope were performed to verify these expressions. From the viscoelastic model relative to acting force between the robot and the colon, a transcendent equation about locomotive efficiency of the critical squirm step was deduced and solved to instruct the design of the robot. Last, in vitro experiments in the fresh colon of a pig were performed. The results show that this kind of microrobot can propel itself freely and reliably in the soft viscoelastic colon. Finally, future areas of research are noted.

Colonic motility diagnosis based on colonic pressure.

Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.

[Prediction and evaluation of heterosis of beef cattle and their application].

The genetic structure and genetic variation of eight beef cattle cross parents populations were analyzed by six microsatellite loci, and heterosis of beef cattle was predicted. On the basis of microsatellite analysis, the effect of 18 cross combinations was estimated by the method of individual animal model BLUP. A new method of molecular quantitative genetics that select best of all cross combination was submitted. The results showed that the combinations with Hereford Limousine and Charolais as paternal parent are better than others in Fengning and Longhua regions; the combinations with Limousine Angus and Hereford as paternal parent are better than others in Zanhuang regions; the combinations with Hereford Limousine and Piemontese as paternal parent are better than others in Funing regions. Effect of three breeds cross is better than two breeds.

[Applications of micromechatronics in minimally invasive surgery].

With the development of Micro Electro Mechanical System(MEMS), it's application in the fields of biomedical engineering becomes a vital consideration. This paper describes the advantages of Minimally invasive Surgery (MIS) and its applications. A novel medical endoscope driven by micro robot is also introduced.

Nerve growth factor induces transcription of the p21 WAF1/CIP1 and cyclin D1 genes in PC12 cells by activating the Sp1 transcription factor.

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by gradually exiting from the cell cycle and differentiating to a sympathetic neuronal phenotype. We have shown previously () that NGF induces the expression of the p21 WAF1/CIP1/Sdi1 (p21) cyclin-dependent kinase (Cdk) inhibitor protein and the G1 phase cyclin, cyclin D1. In this report, we show that induction is at the level of transcription and that the DNA elements in both promoters that are required for NGF-specific induction are clusters of binding sites for the Sp1 transcription factor. NGF also induced a synthetic promoter with repeated Sp1 sites linked to a core promoter, and a plasmid regulated by a chimeric transactivator in which the Gal4 DNA binding domain is fused to the Sp1 transactivation domain, indicating that this transactivation domain is regulated by NGF. Epidermal growth factor, which is a weak mitogen for PC12, failed to induce any of these promoter constructs. We consider a model in which the PC12 cell cycle is arrested as p21 accumulates and attains inhibitory levels relative to Cdk/cyclin complexes. Sustained activation of p21 expression is proposed to be a distinguishing feature of the activity of NGF that contributes to PC12 growth arrest during differentiation

NGF regulates the PC12 cell cycle machinery through specific inhibition of the Cdk kinases and induction of cyclin D1.

We have examined the effects of NGF on components of the PC12 cell cycle machinery. We show that NGF represses over 6-8 d the levels of specific cdk kinase proteins and the G2-M phase specific cyclin B1 and the S phase marker PCNA as well as the level of phosphorylation of the retinoblastoma (Rb) protein. All of these changes may provide a basis for a NGF block to cell cycling. Unexpectedly, the G1 phase-specific cyclin D1 was dramatically increased by inducers of differentiation (NGF and FGF), but not by inducers of proliferation (EGF and insulin). Although the levels of cyclin D1/cdk2 and cyclin D1/cdk4 complexes increased following NGF treatment, as did cyclin D1/Rb complexes, the associated kinase activities declined, indicating that NGF also induces an inhibitor of cdk kinase activity. In agreement, NGF induced the cdk inhibitory protein, p21, which was found in cyclin D1/cdk kinase complexes after NGF treatment. We show that vector over expression of cyclin D1 in PC12 is sufficient on its own to arrest the cells in G1 phase and inhibit expression of PCNA. These results indicate that NGF induction of cyclin D1 and inactivation of cdk kinases, the latter possibly by increase of p21, play a central role in the NGF block of PC12 cell cycling.

Mediation by calcium of thyrotropin--releasing hormone action on the prolactin promoter via transcription factor pit-1.

Mediation by Ca2+ of TRH action on the PRL promoter was investigated by both additivity and pharmacological studies and by techniques that probe more gene-proximal events. TRH required the presence of Ca2+ in the medium for stimulation of transient expression in GH3 cells of a PRL-chloramphenicol acetyltransferase (PRL-CAT) construct containing proximal PRL promoter sequences [(-187)PRL-CAT]. Chronic 12-O-tetradecanoyl phorbol-13-acetate down-regulation of cellular protein kinase C did not block induction of expression of (-187)PRL-CAT by either Ca2+ or TRH. In studies with Ca2+ blockers, the Ca2+ flux inhibitors cobalt ion and nimodipine blocked induction of (-187)PRL-CAT expression by either Ca2+ or TRH. On the other hand, the Ca2+ immobilizers 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyltetraester and 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate blocked induction of expression of this construct by Ca2+ but not by TRH, suggesting that TRH regulation of the PRL promoter may be dependent on Ca2+ fluxes but insensitive to Ca2+ immobilization. We have shown previously that the PRL promoter pit-1 binding site 1P is a TRH response element. In the present studies, Ca2+ regulation studies with 5'-deletion mutants of (-204)PRL-CAT showed that (-75)PRL-CAT, containing the single pit-1 binding site 1P, also contains a Ca2+ response element. The observation that two copies of a site 1P oligomer transferred a Ca2+ response to either of the two minimal constructs (-39)PRL-CAT or (-39)mouse metallothionein-CAT showed that site 1P is an independent Ca2+ response element. Analysis of site 1P mutants yielded a strong correlation between the ability to bind pit-1 and to transfer a Ca2+ response. In addition, coexpression of a mutant pit-1 possessing reduced trans-activational activity strongly inhibited TRH regulation of (-187)PRL-CAT and partially blocked Ca2+ regulation of this construct. We conclude that Ca2+ mediates TRH action on the PRL promoter, and that pit-1 represents a gene-proximal mediator in this signalling pathway.

Thyrotropin-releasing hormone action on the prolactin promoter is mediated by the POU protein pit-1.

TRH is known to regulate transcription of the PRL gene in pituitary cells, but little is known about the mechanism involved. We have characterized TRH response elements (TRHREs) in the promoter region of the rat PRL gene and the gene-proximal protein that transmits the TRH signal to these elements. Exposure of GH3 rat pituitary cells to TRH yielded a large specific stimulation of transient expression of a PRL-chloramphenicol acetyltransferase (PRL-CAT) construct containing the PRL promoter region [(-204)PRL-CAT]. Analysis of 5' deletions of this construct implied that regions -174/-113 and -75/+38 each contain a TRHRE. GH3 cell nuclear extracts are known to footprint four sites, termed, respectively, 1P-4P, on the PRL promoter region. The TRHRE between positions -75/+38 was identified as element 1P, residing at -63/-39, since two copies of a 1P oligodeoxynucleotide transferred a TRH response to either (-39)PRL-CAT or mouse metallothionein-CAT construct (-39)mMT-CAT. Similarly, the more proximal TRHRE may be element 3P, residing at -167/-144, since two copies of this element also transferred a TRH response to (-39)PRL-CAT. Binding of pit-1 to site 1P is known to be capable of activating pituitary cell-specific PRL gene expression. To investigate whether pit-1 can also transduce a TRH signal to this site, oligodeoxynucleotides were prepared corresponding to mutations in either or both of two consensus sequences in site 1P.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antigen signature analysis of dengue-2 viruses strains in Hainan China].

In this paper, we try to define the extent of antigenic variation between dengue-2 viruses from Hainan province, which had been isolated over a period of 3 years (1985-1987). The dengue-2 viruses were compared with the prototype New Guinea B strain and were subjected to antigen signature analysis. Eight strains of dengue-2 virus were analyzed by three monoclonal antibodies: flavivirus group, subcomplex dengue-2 type-specific reactive epitopes, over a range of antigen concentration. Five out of eight dengue-2 virus strains showed them to be antigenically homogeneous, and the remaining three strains showed them to be heterogeneous. Signature analysis provides a rapid and simple means to different strains derived from different sources, thus permit monitoring changes or introductions of hew dengue virus populations in certain geographic region.

The effect of H2O2 upon thioredoxin-enriched lens epithelial cells.

Thioredoxin, a dithiol polypeptide, has been examined as a potential contributor to the recovery of lens epithelial cells from oxidative insult. It is reported that Escherichia coli thioredoxin can (a) effectively reduce lens-soluble protein disulfide bonds generated by H2O2, (b) restore to its initial activity H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase, (c) act as an effective source of reducing potential for lens methionine sulfoxide peptide reductase, and (d) act as a free radical quencher based on studies with a stable free radical system generated by ascorbic acid and 2,6-dimethoxy-p-benzoquinone. Thioredoxin is much more effective than dithiothreitol in restoring glyceraldehyde-3-phosphate dehydrogenase activity and as a cofactor for methionine sulfoxide peptide reductase. Upon incubation with epithelial cells, thioredoxin can be observed in the cell using rocket immunoelectrophoresis. These cells recover from H2O2 insult more rapidly than control cell preparations based upon 1) analyses of plasma membrane-related activities: leucine and 86Rb uptake and 2) analyses of parameters primarily related to the internal cell metabolism: ATP concentration and glyceraldehyde-3-phosphate dehydrogenase activity. Analysis of thioredoxin in cell preparations indicates that only about 9% is in the reduced state implying a low effective concentration of the polypeptide. The experiments suggest that low levels of thioredoxin may significantly increase the ability of lens epithelial cells to recover from exposure to H2O2.

Thioredoxin fragment 31-36 is reduced by dihydrolipoamide and reduces oxidized protein.

The thioredoxin peptide Trp-Cys-Gly-Pro-Cys-Lys, which contains the redox active dithiol, was found to be reduced by lipoamide in a coupled reaction with lipoamide dehydrogenase and NADH. The reduced peptide in turn was shown to reduce insulin, oxidized lens protein and glyceraldehyde-3-phosphate dehydrogenase. While the peptide is not as effective a catalyst for utilizing pyridine nucleotides to reduce protein disulfides as thioredoxin, it offers a system which may be developed to provide more efficient disulfide reduction. This is particularly relevant since no thioredoxin peptides have been found to be active with thioredoxin reductase.

Does elevated glutathione protect the cell from H2O2 insult?

Utilizing glutathione ethyl ester (GSH-EE), the glutathione (GSH) level of lens epithelial cells can be increased as much as 1.9-fold. The epithelial cells maintain the additional GSH in the reduced form. This system was utilized to examine the relative effectiveness of cells with elevated GSH to withstand H2O2 insult. Three parameters were investigated, 86Rb accumulation, a measure of membrane function, ATP levels, an indication of overall metabolism and glyceraldehyde-3-phosphate dehydrogenase (GPD) activity, indicating intracellular enzyme susceptibility to oxidative insult. Under oxidative stress, much of the GSH is in the oxidized form but upon removal of the stress, rapidly returns to the reduced state. However, a loss of approximately 20% in GSH equilibrium levels has been consistently observed. Elevated GSH does not significantly increase the cells' ability to withstand or recover from oxidative stress. Indeed, elevated GSH was found to be somewhat deleterious, causing a decreased ability to recover from oxidative insult. However, in the case of GPD, a significant protection of activity was observed. The overall conclusion is that elevating intracellular GSH concentration does not increase the cells' overall ability to withstand oxidative damage.