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Biomedical subjects

W Fan

Publications and source records attributed to W Fan.

At least 109 records · Page 6Linked to original sources
PubMed1997

5-Fluorouracil interferes with paclitaxel cytotoxicity against human solid tumor cells.

Paclitaxel, a naturally occurring antimitotic agent, has shown efficacy in the treatment of certain solid tumors, particularly metastatic breast carcinoma and drug-refractory ovarian cancers. Recent studies have demonstrated that paclitaxel, in addition to its effects on microtubules and cell cycle arrest, possesses significant cell-killing activity in solid tumor cells by the induction of apoptosis. However, the mechanism by which paclitaxel leads to cell death and its relationship with paclitaxel-induced mitotic arrest is presently unclear. In this study, we attempted to determine whether pre-arresting tumor cells at other phases of the cell cycle could affect paclitaxel-induced apoptosis. We found that 5-fluorouracil (5-FU), another antineoplastic agent that usually arrests tumor cells at the G1-S phase of the cell cycle, could significantly repress the cell-killing activity of paclitaxel in solid tumor cells, even when it was added simultaneously with paclitaxel. Further studies indicated that 5-FU actually inhibits the cytotoxic effects of paclitaxel on both mitotic arrest and apoptotic cell death, suggesting that 5-FU might interfere with paclitaxel cytotoxicity at an early stage, probably by preventing tumor cells from entering G2-M phase. Because recent clinical trials have used a combination of paclitaxel and 5-FU in the treatment of metastatic breast cancers, our results also suggest that the combination of these two drugs might not be as valuable in clinical chemotherapy.

Antimetabolites, Antineoplastic↗
PubMed1996

Charge-burping theory correctly predicts optimal ratios of phase duration for biphasic defibrillation waveforms.

BACKGROUND: For biphasic waveforms, it is accepted that the ratio of the duration of phase 2 to the duration of phase 1 (phase-duration ratio) should be < or = 1. The charge-burping theory postulates that the beneficial effects of phase 2 are maximal when it completely removes the charge delivered by phase 1. It predicts that the phase-duration ratio should be < 1 when the time constant of the defibrillation system (tau s) exceeds the time constant of the cell membrane (tau m) but > 1 when tau s < tau m. This study tested the hypothesis that the optimal phase-duration ratio depends on tau s (the product of the defibrillator capacitance and pathway resistance). METHODS AND RESULTS: In a canine model of transvenous defibrillation (n = 8), we determined stored-energy defibrillation thresholds (DFTs) for biphasic waveforms from conventional capacitors (140 microF. tau s = 7.1 +/- 0.8 ms) and very small capacitors (40 microF. tau s = 2.0 +/- 0.2 ms). Each capacitance was tested with phase-duration ratios of 0.5, 1, 2, and 3. The duration of phase 1 approximated the optimal monophasic waveform, 6.3 +/- 0.7 ms for 140-microF waveforms and 2.8 +/- 0.2 ms for 40-microF waveforms. For 140-microF waveforms, the DFT was lower for phase-duration ratios < or = 1 than for phase-duration ratios > 1 (P = .0003). The reverse was true for 40-microF capacitors (P = .0008). There was a significant interaction between the effects of capacitance and phase-duration ratio on DFT (P = .0002). The lowest DFT for 40-microF waveforms was less than the lowest DFT for 140-microF waveforms (4.9 +/- 2.5 versus 6.4 +/- 2.4 J, P < .05). CONCLUSIONS: The optimal phase-duration ratio is < or = 1 for conventional capacitors and > 1 for small capacitors. This supports the predictions of the charge-burping theory.

Animals↗
PubMed1996

Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line.

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb is widely expressed in human tissues and cells, but gag-pol mRNA has not been found. Further, the env gp70 gene contains an open reading frame throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so far is in placenta and the lowest in cytotrophoblasts and choriocarcinoma cell lines. In this report we have studied ERV3 mRNA and protein expression in the human monoblastic cell line U-937 during differentiation into monocytes/macrophages. Differentiation of U-937 cells was induced by 1,25a-dihydroxyvitamin D3 (vitD3), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The expression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic development. Using TPA, the expression of ERV3 env was detected as 9- and 3.5-kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Induction with vitD3, IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represents an excellent model system for further studies to study the relationship between ERV3 expression and cellular differentiation.

Calcitriol↗
PubMed1996

Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids. The normal transcript appears to be abundantly expressed in the hypothalamus, a region of the brain involved in body weight regulation. Variation in the relative abundance of alternative splice products is observed between inbred mouse strains and appears to correlate with an intron length polymorphism. This allele of tub is a candidate for a previously reported diet-induced obesity quantitative trait locus on mouse chromosome 7.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Müller and RPE cell response to photoreceptor cell degeneration in aging Fischer rats.

With increasing age, retinas of male Fischer rats gradually lose photoreceptor cells beginning at the ora serrata and extending to the central retina resulting in a pronounced peripheral retinopathy. In this study, we used immunocytochemical methods for glial fibrillary acidic protein (GFAP) and carbonic anhydrase II (CA II) to study the Müller cell response to age-related photoreceptor cell degeneration in the superior retina. Retinas of Fischer rats were also examined by electron microscopy to investigate retinal pigment epithelial (RPE) cell and Bruch's membrane structural changes with advancing age. Our study showed extensive photoreceptor cell loss in the region of the ora serrata beginning by 16 months, while few photoreceptor cells were found at 23 months. Neovascularization also occurred in the area of the peripheral retinopathy at the level of the RPE cells as determined by electron microscopy, as well as a thickening of Bruch's membrane with initial signs of small breaks. Dense areas of GFAP-immunostaining of Müller cell processes were found in the superior peripheral retina of 16-30 month-old rats where photoreceptor cells were degenerating. After 21 months, Müller cell processes extended into the subretinal space. However, in the central retina, where the photoreceptor cell population was more stable, GFAP-immunolabelled Můller cells were not detected. Immunoblots of retinal homogenates confirmed elevated GFAP levels at 18-30 months when compared to homogenates from retinas of 6-month-old Fischer rats. During photoreceptor cell degeneration, Müller cell processes were also prominently immunostained for CA II, which were seen to occupy the subretinal space at 18-30 months. Our results suggest that Müller cells respond to the age-related peripheral retinopathy in Fischer rats by increasing GFAP content and growth of their processes into the subretinal space to form a glial scar, but only in the area of severe photoreceptor cell loss. In addition, RPE and Bruch's membrane of aged retinas exhibit typical early age-related changes as also reported for aged human eyes.

Aging↗
PubMed1996

Identification of seven new human MHC class I region genes around the HLA-F locus.

Using cDNA hybridization selection techniques, we identified seven new genes in a 280 kilobase YAC covering the HLA-F locus. The new genes were mapped back to the YAC by a combination of optical restriction mapping and pulse field gel electrophoresis. Northern analysis of individual clones demonstrated the presence of either different mRNA sizes or different expression patterns. Two of the cDNA clones were expressed only in lymphoid cell lines: one in Jurkat cells (T cell) and another in JY cells (B cell). All the genes lacked sequence similarity to any known classical and non-classical major histocompatibility complex (MHC) class I genes, indicating that the MHC class I region has more functions than anticipated. Of the seven new genes, one is highly similar (97%) to mouse 60S ribosomal protein, and another is homologous to diubiquitin proteins. Of the two G-coupled receptor-like cDNAs, one was fully sequenced and found to be an olfactory receptor-like gene. The study strengthens evidence that the MHC complex not only plays a key role in the immune system, but also contributes to non-immunological functions.

Animals↗
PubMed1996

Recurrent appearance of protective zones after an unsuccessful defibrillation shock.

This study was designed to test the hypothesis that protective zones appear recurrently at the initiation of ventricular fibrillation (VF) and that when shocks are delivered during protective zones, there can be a decrease in the defibrillation energy requirement. A total of 12 open-chest dogs were studied. Six dogs were included in protocol 1. After eight baseline pacing stimuli (S1) with cycle lengths of 300 ms, a strong premature stimulus (S2) (73 +/- 10 mA) was given to induce VF. In subsequent episodes, a second strong premature stimulus (S3) was given at progressively longer S2-S3 intervals in 20-ms increments. In protocol 2, we delivered unsuccessful defibrillation shocks via a transvenous defibrillation electrode placed in the right ventricular apex of six dogs. A second shock was then delivered to patch electrodes on the right ventricular outflow tract and the posterior wall of the left ventricle. The results of protocol 1 showed that the S3 terminated reentry and prevented VF only when it occurred at specific time intervals after the S2 (the protective zones). These protective zones appear recurrently up to 375 ms after the onset of VF. The results of protocol 2 showed that the total energy required for successful defibrillation was dependent on the interval between the first and second shocks. Intervals favoring effective defibrillation (protective zones) appeared recurrently for up to 280 ms after the first shock. When the second shock was delivered during a protective zone, the defibrillation energy requirement was decreased by up to 23% (from 13.1 +/- 2.0 to 10.1 +/- 1.8 J, P < 0.003). However, when the shock was delivered outside the protective zone, a significant increase in the defibrillation energy requirement was observed. We conclude that protective zones appear recurrently at the onset of VF and after unsuccessful defibrillation shocks.

Animals↗
PubMed1996

Baroreflex frequency-response characteristics to aortic depressor and carotid sinus nerve stimulation in rats.

Dynamic cardiovascular regulation depends on baroreflexes and the processing of sensory information. We evaluated the influence of choice of anesthetic on the frequency-response characteristics of the baroreflex of rats by electrical stimulation of two major baroreceptor-containing nerves, the carotid sinus (CSN) and aortic depressor nerves (ADN). The ADN contains baroreceptors alone, and the CSN has both chemoreceptors and baroreceptors. Most studies were performed under pentobarbital sodium (PB; 65 mg/kg) anesthesia. We compared this to a combination of alpha-chloralose (80 mg/kg) and urethan (800 mg/kg) (CU). Stimulus trains were fixed at 60-s periods (0.1-ms shocks, supramaximal intensities, 1-200 Hz) and delivered in steady and burst patterns. Unilateral steady-frequency ADN stimulation in PB-anesthetized rats evoked reflex decreases in mean arterial pressure and heart rate that increased with frequencies between 1 and approximately 10 Hz before reaching a maximum. From 10 to 200 Hz, PB ADN reflex responses were sustained at these maximal levels. Cutting the opposite ADN or both CSNs did not alter ADN baroreflex relationships. Heart rate and mean arterial pressure depressor responses evoked by CSN stimulation in PB-anesthetized rats were smaller compared with ADN stimulation and were biphasic, with small pressor responses at 1 Hz. Maximal CSN depressor responses in PB-anesthetized rats occurred at approximately 20 Hz and were sustained at 20-200 Hz. Baroreflex responses for ADN stimulation in CU-anesthetized rats were similar to those in PB-anesthetized rats. In contrast, in CU-anesthetized rats, maximal CSN responses occurred at 20 Hz but declined at 50-200 Hz. Constant- and burst-stimulation responses were equivalent. The results suggest that rat aortic baroreflex responses are sustained even at very high input frequencies (> 100 Hz). The sustained high-frequency baroreflex responses seem to present a paradox in understanding central integration because other studies show substantial depression of sensory transmission at the first synapse in the nucleus tractus solitarius at frequencies as low as 10 Hz.

Animals↗
PubMed1996

Reentrant wave fronts in Wiggers' stage II ventricular fibrillation. Characteristics and mechanisms of termination and spontaneous regeneration.

The mechanisms of Wiggers' stage II ventricular fibrillation (VF) are poorly understood. Using computerized mapping techniques, we studied the patterns of activation during Wiggers' stage II VF in 13 open-chest dogs. In 7 of the 13 dogs, the right ventricular Purkinje fibers and adjacent subendocardial myocytes were ablated with Lugol solution. VF was induced electrically, and 3 to 5 seconds of data were obtained beginning approximately 2.5 seconds after the onset of VF. Dynamic displays of the activation patterns and isochronal maps revealed the presence of reentrant wave fronts in 17 of 33 runs of VF in ablated ventricles and in 12 of 45 runs of VF in intact ventricles. The incidence of reentry was not different between the subendocardium-ablated group versus the nonablated group (1.7 +/- 1.6 versus 1.2 +/- 1.6 rotations per episode of VF, P = .19). There were no differences in the core size (25 +/- 19 versus 29 +/- 18 mm2), life span (3.4 +/- 1.1 versus 3.2 +/- 1.2 rotations), or cycle length (111 +/- 12 versus 107 +/- 8 ms) in ablated ventricles versus intact ventricles, respectively. The core was unstable as it meandered within the mapped area displacing the entire reentrant wave front. In all episodes, the reentrant wave fronts were spontaneously initiated by an interaction between two propagating wave fronts roughly perpendicular to each other. The second wave front met the tail of the first wave front 69 +/- 11 ms (range, 40 to 90 ms) after its latest activation, indicating that the interaction occurred during a vulnerable period. The reentrant wave fronts terminated spontaneously (n = 7), as the result of interference by an invading wave front (n = 19 or meandered off the mapped region (n = 3). We conclude the following: (1) Reentrant activities with short life spans and meandering cores are present during Wiggers' stage II VF in dogs. (2) New reentrant wave fronts are generated when one wave front interacts with another wave front during its vulnerable period. (3) The reentrant wave fronts terminate spontaneously or as the result of interference. (4) Chemical subendocardial ablation does not affect the incidence, life span, cycle length, or core size of the reentrant wave fronts.

Animals↗
PubMed1996

Photoreceptor repair in response to RPE transplants in RCS rats: outer segment regeneration.

PURPOSE: We have previously shown that transplants of normal rat neonatal RPE cells rescued photoreceptor cells in retinas of Royal College of Surgeons (RCS) dystrophic rats for up to one year. In this study, we investigated the photoreceptor rescue effects in RCS rats within the first three weeks following transplantation in an attempt to determine if RPE transplants initiate repair mechanisms, specifically, outer segment (OS) regeneration. METHODS: Freshly isolated RPE cells from neonatal pigmented Long Evans rats were transplanted into the subretinal space of 22-23 day-old RCS rats using a transscleral approach. For controls, vehicle was similarly injected. RESULTS: When analyzed at 10 days post-transplantation, long inner segments were observed with short buds of outer segment growth in the area of the RPE-cell transplants. The outer segments were of insufficient length to be measured at 10 days, but by 14 and 21 days, OS were 2.02 +/- 0.32 microns and 18.80 +/- 2.78 microns, respectively. In vehicle-injected retinas from 10 to 21 days postsurgery, outer segments were not observed and the inner segments were three-fold shorter than in RPE-transplanted retinas. At 10 days post-transplantation, most RPE cells were seen in the subretinal space, but a few had attached to Bruch's membrane; however, by 21 days, many of the transplanted RPE cells had attached to Bruch's membrane, although a few were found free in the subretinal space. CONCLUSIONS: This study has shown that transplants of normal rat neonatal RPE cells have the capacity to support not only photoreceptor cell survival but also initiate early repair mechanisms as exhibited by outer segment regeneration in RCS retinas. These results also conclusively show the important role that the RPE plays in outer segment growth and maturation.

Animals↗
PubMed1996

[Combustion under microgravity and technique of fire prevention and suppression in space cabin].

This is a brief review on microgravity combustion, along with the discussion of the fundamental characteristics of combustion and fire processes under microgravity. Recent research activities in microgravity combustion and space fire prevention were emphasized. In addition, the potential use of flame-inhibiting atmospheres in the space cabin was introduced. The technique of fire detection and extinguishment in spacecraft environments was also discussed.

Fire Extinguishing Systems↗
PubMed1996

[The trend of changes in etiologic types of heart diseases in Shanghai from 1948 to 1989].

Analysis of the data from 7188 cases seen in the 1980s two general hospitals in Shanghai and comparison of the data with those in the 1950s, 1960s and 1970s revealed that the percentage of heart diseases among the inpatients in medical wards increased in each decades, from 9.89%, 15.69% 20.91% to 23.54% respectively. The constituent ratios of different etiologic types of heart diseases changed. Coronary heart disease constituted the largest proportion, next in number was rheumatic heart disease and congenital heart disease was in the third place. The incidence of congenital heart diseases, myocarditis, cardiac dysrhythmias without organic heart diseases, cardiomyopathy and endocarditis increased and that of rheumatic heart disease, pulmonary heart disease and hypertensive heart disease apparently decreased, syphilitic heart disease was rarely encountered.

Adolescent↗
PubMed1995

Olfactory receptor-like genes are located in the human major histocompatibility complex.

The murine major histocompatibility complex (MHC) includes sequences that are responsible for haplotype-specific odor types that, in turn, influence mating preference. We report that there are several olfactory receptor genes or pseudogenes in the Class I region of the human MHC. At least one of these genes is intact, appears to encode an mRNA, and is quite homologous to a previously reported murine olfactory receptor.

Amino Acid Sequence↗
PubMed1995

Detection of herpes simplex and varicella-zoster infection from cutaneous lesions in different clinical stages with the polymerase chain reaction.

BACKGROUND: The polymerase chain reaction (PCR) can be used to diagnose a variety of infectious processes. OBJECTIVE: We sought to determine whether Tzanck smear debris, vesicle fluid swabs, crusts, or fixed tissue specimens are the best source for template herpes simplex virus (HSV) or varicella-zoster virus (VZV) DNA for the PCR. METHODS: Patients with both clinical and histologic evidence of HSV (n = 6) or VZV (n = 16) infection were examined. Stained Tzanck smears, vesicle fluid swabs, dried crusts, and skin biopsy specimens were obtained at the same time from each patient. DNA was extracted from the different clinical specimens and then examined for HSV or VZV DNA with PCR. Fifteen control subjects did not have clinical or histologic evidence of herpesvirus infection. RESULTS: In cases of suspected VZV infection, PCR detected VZV DNA sequences from all 15 Tzanck smears, all 15 vesicle swabs, one of one crust, and 14 of 16 fixed tissue specimens. HSV DNA sequences were detected from all six Tzanck smears, all four vesicle fluid swabs, two of two crusts, and five of six fixed tissue specimens. CONCLUSION: PCR can detect VZV and HSV DNA sequences from a variety of sources including formalin-fixed tissue specimens. Although viral DNA was detected slightly more frequently from Tzanck smear debris, crusts, and vesicle fluid swabs compared with fixed tissue specimens, each was an excellent source of target DNA for the PCR to confirm the diagnosis of herpesvirus infection.

Chickenpox↗
PubMed1995

Effects of the pacing site, procainamide, and lead configuration on the relationship between the upper limit of vulnerability and the defibrillation threshold.

In six open chest dogs, we determined the upper limit of vulnerability (ULV) and defibrillation threshold (DFT) by an up-down algorithm when the pacing site was at the right atrium, at the left ventricular apex, and at the left ventricular base. Monophasic shocks (6 ms) were given to epicardial patches at 20 and 40 ms before the peak of the T wave to bracket the mid-upslope. In an additional six closed-chest dogs, we determined the ULV and the DFT with transvenous leads with an 8-ms biphasic waveform. The S1 pacing site was at the right ventricular apex and the right atrium, and the shocks were given at 20 ms and 40 ms before the peak of the T wave, and on the peak of T wave. The same test was repeated after intravenous procainamide infusion (20 mg/Kg loading, then 2 mg/min maintenance). In the first six dogs, the ULV determined when pacing was given to the left ventricular apex, the left ventricular base, and the right atrium was 4.2 +/- 1.7 J, 4.4 +/- 2.1 J, and 3.9 +/- 1.5 J, respectively; values that were not significantly different from the DFT of 4.8 +/- 1.9 J, 4.5 +/- 1.9 J, and 4.2 +/- 1.3 J, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1995

[Experimental and clinical study on pneumocystosis. IV. Use of a 4D7 monoclonal antibody to detect Pneumocystis carinii by immunoperoxidase staining].

This paper reports on the diagnostic utility of the 4D7 monoclonal antibody (McAb) and immunohistochemical (IHC) staining to detect P. carinii. Specimens of 30 pathological sections of lung tissues and 1 smear of aspirated bronchial material from confirmed cases, and 12 sputum smears from high risk patients with pneumonia were examined by immunohistochemical method using the 4D7 McAb. The results showed that both the sensitivity and specificity of the 4D7 McAb-IHC staining were 100% (31/31). A comparison between immunohistochemical staining with GMS and TBO staining was made, no difference in sensitivity was found. However, the IHC method gave a clear back ground that is useful for definite diagnosis.

Antibodies, Fungal↗