Biomedical subjects

H Gao

Publications and source records attributed to H Gao.

299 records · Page 17Linked to original sources

PubMedDate not supplied

Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus.

A comparative study of the expression of metabotropic glutamate receptor 2/3 (mGluR2/3) was done in the hippocampus of rats and mice after pilocarpine-induced status epilepticus (APISE), and of patients with mesial temporal lobe epilepsy. At 1 day APISE, there was a marked increase in mGluR2/3 immunoreactivity in the stratum lacunosum moleculare (SLM) of CA1 area and in the middle one-third of the molecular layer (MM) of the dentate gyrus. Immuno-electron microscopic study showed degenerating mGluR2/3 positive axons in the SLM of CA1 area at 1 day APISE. From 7 days, mGluR2/3 immunopositive product decreased, and by 31 days APISE, it almost disappeared in two-thirds of the SLM near CA2. In the mouse model at 2 months APISE, mGluR2/3 immunopositive product in two-thirds of the SLM near the stratum radiatum disappeared, and so did in the whole SLM of CA1 area in patients with mesial temporal lobe epilepsy. Neuropharmacological study by intravenous injection of mGluR2/3 agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC] at different doses at 1h during pilocarpine induced status epilepticus showed that (2R,4R)-APDC could not stop seizures and neuronal death in the hilus of the dentate gyrus. The present study, therefore, suggests that the reduction of mGluR2/3 immunopositive product in the SLM of CA1 is a consequence of neuronal loss in either the entorhinal cortex or CA1 area of the hippocampus, and at the dosage range from 12.5 to 600 mg/kg, (2R,4R)-APDC may not be effective in the prevention of seizures or neuronal death in the hilus of the dentate gyrus.

Animals↗

PubMedDate not supplied

Double-stranded cyclic oligonucleotides with non-nucleotide bridges.

A series of double-stranded, cyclic oligodeoxynucleotides with non-nucleotide bridges have been synthesized, and their physicochemical properties and susceptibility to enzymes have been investigated. These bridged duplexes are of potential interest for their binding properties to transcription factors and other DNA-binding proteins. Triethylene glycol has been employed as the bridge to alter the lipophilicity of the duplex and avoid the potential for enzymatic cleavage. The synthetic route involved the synthesis of a 3'-phosphorylated, nicked double-stranded precursor with the final internucleotide bond being formed chemically using a water soluble carbodiimide. These bridged duplexes have high thermal dissociation temperatures, and the Tm for a triethylene-bridged 20 base pair duplex was higher than that for the corresponding pentathymidylate-bridged duplex. EcoR I endonuclease cleaved a ligated, bridged duplex at a slower rate than the corresponding unmodified duplex, whereas the unligated, bridged duplex was cleaved more rapidly. Sufficient amounts of the bridged octamer and dodecamer were prepared for proton NMR spectroscopic studies, and 2D COSY and NOESY spectra were obtained. The results indicate that the ligated duplex has a B-form conformation.

Base Sequence↗

PubMedDate not supplied

Application of BCUT metrics and genetic algorithm in binary QSAR analysis.

The application of three-dimensional H-suppressed BCUT metrics (BCUTs) in binary QSAR analysis was investigated using carbonic anhydrase II inhibitors and estrogen receptor ligands as test cases. Variable selection was accomplished with a genetic algorithm (GA). Highly predictive binary QSAR models were obtained for both sets of compounds within 200 GA generations. The derived binary QSAR models were validated with two sets of compounds not included in the training sets. The results indicate that BCUTs are very useful molecular descriptors, and the genetic algorithm is a very efficient variable selection tool in binary QSAR analysis.

Algorithms↗

PubMedDate not supplied

Binary quantitative structure-activity relationship (QSAR) analysis of estrogen receptor ligands.

The use of high throughput screening (HTS) to identify lead compounds has greatly challenged conventional quantitative structure-activity relationship (QSAR) techniques that typically correlate structural variations in similar compounds with continuous changes in biological activity. A new QSAR-like methodology that can correlate less quantitative assay data (i.e., "active" versus "inactive"), as initially generated by HTS, has been introduced. In the present study, we have, for the first time, applied this approach to a drug discovery problem; that is, the study of the estrogen receptor ligands. The binding affinities of 463 estrogen analogues were transformed into a binary data format, and a predictive binary QSAR model was derived using 410 estrogen analogues as a training set. The model was applied to predict the activity of 53 estrogen analogues not included in the training set. An overall accuracy of 94% was obtained.

Cluster Analysis↗

PubMedDate not supplied

Comparison of binary and 2D QSAR analyses using inhibitors of human carbonic anhydrase II as a test case.

Binary and conventional 2D QSAR have been derived for a set of carbonic anhydrase II (CA II) inhibitors. An overall predictive accuracy of 94% was obtained by binary QSAR and of 84% by 2D QSAR model. For both models, preferred molecular descriptor sets were identified, which were overlapping but not identical. Both binary and 2D QSAR captured important molecular features of CA II inhibitors, notably the presence of a sulfonamido group, which is critical for binding, but also hydrophobicity. Promising results were obtained when the derived QSAR models were used to test a set of CA II inhibitors not included in the training set. In binary QSAR, previously unobserved boundary effects were detected both in the analysis of known inhibitors and when screening a large combinatorial library for putative inhibitors. The complementary use of binary and conventional 2D QSAR is thought to increase the accuracy of the lead discovery process by QSAR techniques.

Carbonic Anhydrase Inhibitors↗

PubMedDate not supplied

Changes in activity of energy dissipating mechanisms in wheat flag leaves during senescence.

Excitation energy dissipation, including the xanthophyll cycle, during senescence in wheat flag leaves grown in the field was investigated at midday and in the morning. With progress of senescence, photosynthesis (Pn) and actual PSII photochemical efficiency (PhiPSII) decreased markedly at midday. The decrease in extent of Pn was greater than that of PhiPSII. However, there was no significant decline in Pn and PhiPSII observed in the morning, except in leaves 60 days after anthesis. The kinetics of xanthophyll cycle activity, thermal dissipation (NPQ), and q (f) observed at midday during senescence exhibited two distinct phases. The first phase was characterized by an increase of xanthophyll cycle activity, NPQ, and q (f) during the first 45 days after anthesis. The second phase took place 45 days after anthesis, characterized by a dramatic decline in the above parameters. However, the qI, observed both at midday and in the morning, always increased along with senescence. A larger proportion of NPQ insensitive to DTT (an inhibitor of the de-epoxidation of V to Z) was also observed in severely senescent leaves. In the morning, only severely senescent leaves showed higher xanthophyll cycle activity, NPQ, q (f), and qI. It was demonstrated that, at the beginning of senescence or under low light, wheat leaves were able to dissipate excess light energy via NPQ, depending on the xanthophyll cycle. However, the xanthophyll cycle was insufficient to protect leaves against photodamage under high light, when leaves became severely senescent. The ratio of (Fj - Fo)/(Fp - Fo) increased gradually during the first 45 days after anthesis, but dramatically increased 45 days after anthesis. We propose that another photoprotection mechanism might exist around reaction centres, activated in severely senescent leaves to protect leaves from photodamage.

Aging↗

PubMedDate not supplied

In vitro assessment of the Milwaukee Heart and right to left balance.

A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results.

Biomechanical Phenomena↗

PubMedDate not supplied

The impact of residual renal function and total body water volume on achieving adequate dialysis in CAPD.

AIMS: The objective is to evaluate the impact of residual renal function (RRF) and total body water (TBW) on achieving adequate dialysis. METHODS: Sixty three CAPD patients performing four 2 liter exchanges daily were evaluated for RRF, total weekly Kt/V (TWKt/V), total weekly creatinine clearance (TWCC) and TBW. RESULTS: In patients with residual renal function (N = 41), TWKt/V and TWCC were 2.2 +/- 0.8 and 77.4 +/- 24.5 L, respectively. In patients without RRF (N = 22), TWKt/V was 1.6 +/- 0.4 and TWCC 42.6 +/- 9.2 L. TBW correlated negatively with TWKt/V in the group without RRF (r = -0.75, P<0.001). CONCLUSION: It is not possible for larger patients without RRF treated with CAPD (2L x 4 exchanges) to achieve the acceptable targets for TWKt/V and TWCC due to TBW.

Adult↗

PubMedDate not supplied

Nonsmall cell lung adenocarcinoma metastatic to the vitreous without fundus lesions.

A 76-year-old man presented with vitritis in the absence of visible fundus lesions. Vitreal cytologic analysis revealed adenocarcinoma; immunostaining was consistent with a pulmonary origin. This case highlights the need to exclude metastasis to the vitreous in a patient with an oncologic history, even in the absence of visible posterior segment lesions. It also illustrates the utility of immunostaining to better determine the tissue of origin when a metastatic lesion is encountered.

Adenocarcinoma↗

PubMedDate not supplied

Transitional mucosa at anastomosis. A cause of local tumor recurrence in patients with rectal cancer after anterior resection.

Transitional mucosa adjacent to colorectal cancers is essentially characterized by an excess of sialomucins at the expense of the normally predominant sulphomucins in epithelial cells lining the intestinal crypts which presents the early stage of oncogenic transformation of colorectal epithelium. The presence or absence of sialomucins at the resection margins was studied histochemically using the high iron diamine-alcian blue(HID-AB) stain in 64 rectal cancer patients in Dukes' B stage who underwent curative anterior resection. The correlation was revealed between the presence of sialomucins at the resection margins and subsequent development of local tumour recurrence. Fourteen of 27 patients (51.9%) with sialomucins predominant pattern at either resection margin developed local recurrence compared with 4 of 37 patients (10.8%) with sulphomucins predominant pattern (P less than 0.001). It is suggested that determination of the transitional mucosa around anastomosis in patients treated for the rectal carcinoma by anterior resection appears to identify those with a higher risk of local recurrence.

Adenocarcinoma↗

PubMedDate not supplied

Application of a new nuclear scintigraphy camera to evaluate flow and mechanical pumping of artificial hearts.

To assist in the development of an artificial blood pump, The Milwaukee Heart (MH-1), a new nuclear scintigraphy camera was used to study the wash-in and wash-out patterns of the MH-1. These studies indicate the MH-1 has an ejection fraction of 59.3%, with a stroke volume of 72 +/- 3 ml, and an afterload of 130 mmHg. Flow through the device is highly uniform, with no areas of stagnation. Regional ejection fraction images demonstrate homogeneous ejection from apex to base. The ability to scan through the first pass images allows study of wash-in, mixing, and wash-out of the tracer. In conclusion, this technique may provide a new approach to evaluating artificial heart pumps.

Blood Flow Velocity↗