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Biomedical subjects

B Chen

Publications and source records attributed to B Chen.

569 records · Page 32Linked to original sources

Low-dose vaccinia virus-mediated cytokine gene therapy of glioma.

Recombinant viruses can produce cytokines in tumors mobilizing an immune response to tumor cells. In this study, the authors investigated gene expression, in vivo antitumor efficacy, and safety of attenuated recombinant vaccinia virus (rVV) carrying murine cytokine genes interleukin (IL)-2 (rVV-mIL-2), IL-12 (rVV-mIL-12), and both IL-2 and IL-12 (rVV-2-12) in an athymic nude mice model. Significant tumor inhibition (p < 0.05) was observed in a preestablished subcutaneously implanted C6 glioma model using rVVs at doses ranging from 10(2) to 10(7) plaque forming units (PFU). An antitumor effect did not depend on the dose of the rVV-mIL-2 and rVV-mIL-12 viruses. All constructed rVVs induced a high level of cytokine expression in vitro and in vivo. Most groups injected with high doses of recombinant viruses encoding cytokine genes (10(5) to 10(7) PFU) showed signs of cytokine toxicity, whereas in the low-dose treatment groups (10(2) to 10(3) PFU) toxicity was greatly reduced. The antitumor activity of rVV-mIL-12 was associated with increases in both the percentage and number of natural killer T cells in the spleen. Local detection of interferon-y and tumor necrosis factor-alpha was also correlated with tumor growth arrest induced by the treatment. High-dose VV control vector per se induced tumor inhibition by activating Mac-1+ cells in blood, but the antitumor effect was less pronounced compared with rVV-carrying cytokine genes (p < 0.05). These results suggest that attenuated recombinant strains of VV at low doses may potentially be efficient vectors for cancer immunotherapy.

Animals↗

Public health impact of genetic tests at the end of the 20th century.

PURPOSE: To evaluate genetics tests available for clinical, research, and public health purposes in terms of their public health impact as measured by the number of people who could potentially be tested. METHODS: Genetic tests for the 751 inherited diseases or conditions listed in the GeneTests database as of November 2000, were classified on the basis of their use for population-based testing and the prevalence of the disease or condition being tested. The GeneTests database divides the tests into two groups: those offered for clinical use and those available for research only. RESULTS: Of the 423 clinical tests, 51 had potentially greater impact on public health because of their use in statewide newborn screening programs, other population screening programs, or testing for common diseases with a prevalence over 1 in 2,000 people. Among the 328 tests performed for research purposes only, 18 met the criteria for potentially greater public health impact. CONCLUSIONS: Our classification scheme indicated that fewer than 10% of the genetic tests listed in the GeneTests database at the end of 2000 are highly relevant to public health. The majority of genetic tests are used in diagnosis and/or genetic counseling for rare, single-gene disorders in a limited number of people. However, as more tests are being considered for newborn screening, and associations between genes and common diseases are being discovered, the impact of genetic testing on public health is likely to increase.

Databases, Genetic↗

Mitochondrial polymorphisms as risk factors for endometrial cancer in southwest China.

It is just in recent years that mitochondrial DNA (mtDNA) mutations have been found in solid tumors. Although a direct link between the presence of mtDNA mutations and the development of tumors has not been made, mtDNA mutations might prove significant in the detection of tumor recurrence and possibly in the detection of genotoxic damage. To investigate the relationship between mtDNA variation and endometrial cancer, we collected blood samples from subjects with Han native background in Yunnan province in China, 49 of them with pathologically conformed endometrial cancer and 31 as controls with no cancer disease and sequenced two hypervariable segments of control region, part of 16sRNA gene, tRNA(leu) (tRNA is transfer RNA) gene and ND1 gene of mtDNA and identified some diagnostic polymorphisms by restriction fragment length polymorphism of coding region of mtDNA. We could not identify the suspected mutations that are related to diabetes and obesity from our endometrial cancer patients. However, our data showed that patients with endometrial cancers clustered in haplogroup D in a significantly higher frequency when compared with controls, implicating a possible association of haplogroup D to endometrial cancer. We concluded that mitochondrial polymorphisms in haplogroup D might play a genetic role in predisposing to endometrial cancer.

Case-Control Studies↗

Using sandpaper for noninvasive transepidermal optical skin clearing agent delivery.

We present a gentle mechanical method for the noninvasive transepidermal delivery of topically applied optical skin clearing agents. Optical skin clearing reduces light scattering in highly turbid skin with the aid of hyperosmotic chemicals such as glycerol, polyethylene glycol, and solutions of dextrose. Transepidermal delivery of such agents is believed to be most patient compliant and most likely to be used in a clinical environment. Optical skin clearing has the potential to expand the current limited use of laser light in medicine for diagnostic and therapeutic applications. Light scattering limits the penetration depth of collimated light into skin. In order to increase the diffusion of topically applied optical skin clearing agents into skin, we present a gentle mechanical delivery method involving glycerol and dextrose as optical skin clearing agents and fine 220-grit sandpaper to rub the clearing agent into the tissue. Gentle rubbing causes abrasion of the superficial skin layer including the stratum corneum, which otherwise prevents these optical skin clearing agents from freely diffusing into skin. Results indicate very fast optical skin clearing rates. In vivo hamster skin turned transparent within 2 min. The 1e light penetration depth increased by 36+/-3.75% for dextrose and 43+/-8.24% for glycerol. Optical skin clearing was reversed using phosphate buffered saline solution. Skin viability was observed 70 h post-treatment and showed scabbing and erythema on a few percent of the total optically cleared skin surface.

Administration, Cutaneous↗

Otoscopy and photography: a new method.

A new hand-held otoscope photographic system, convenient and suitable for clinical application, is introduced. This instrument allows clear otoscopic examination in stenotic or tortuous ear canals, and photographs the subject in one procedure. The instrument consists of a rod-lens optical system, a fiberoptic light source, a camera, and exchangeable speculum and a strobe light. Color photographs of tympanic membranes and middle ear pathology are presented.

Ear Canal↗

The change of C-fos expression in ovariectomized rats following electroacupuncture treatment--an immunohistochemistry study.

The roles of electroacupuncture (EA) in regulating the function of ovulation in rat have been investigated; however, the systematic study for the involvement of neural population of central nervous system (CNS) in acupuncturing the ovariectomized rat for promoting functional recovery has not been well understood. The present research was designed to examine, by C-fos immunocytochemistry, the distribution of Fos labelled neuron in CNS after acupuncturing the point of "Zhong-Ji (RN3)", "Guan-Yuan (RN4)", "San-Ying-Jiao (SP6)" and "Zi-Gong (EXCA1)" in ovariectomized rat. The area occupied by Fos protein labelled neuron, two hours after ovariotomy, was detected in medial preoptic nucleus (MPN), lateral preoptic nucleus (LPN), suprachiasmatic nucleus (SCN), paraventricular nucleus of the hypothalamus (PANH), medial amygdala nucleus (MAN), periventricular nucleus of the hypothalamus (PVNH), ventromedial nucleus of the hypothalamus (VNH), and arcuate nucleus (AR). The C-fos immunoreactive labelled neurons disappeared two weeks later following ovariotomy. The rat, recovering for two weeks after ovariotomy, received EA, and many specific Fos labelled cell were observed in LPN, PVNH, VNH, SCN and especially in AR, PANH and MPN, but not any labelled neuron could be found in MAN. No obvious C-fos expression was shown in these areas in the control group and EA group without ovariotomy. These results indicate that the above structures involved in regulating the function of hypothalamus-pituitary-ovarian axis and EA could modulate this function through effects on the above nuclei.

Animals↗

Antitumor effect of IL-2, p53, and bax gene transfer in C6 glioma cells.

The use of interleukin-2 (IL-2) and p53 for immunotherapy and gene therapy for cancer has shown promising results. In this study, we examined the efficacy of plasmid gene therapy utilizing murine IL-2, the wild-type (wt) human p53 gene, the combination of these genes, and the murine bax gene, which are under the control of the cytomegalovirus (CMV) immediate-early promoter, in nude mice bearing established subcutaneous C6 glioma. In vitro assays and immunocytochemical analysis for therapeutic genes demonstrated expression of the proteins in C6 transfected cells. In animal studies, significant antitumor activity was observed for the IL-2, p53/IL-2, and bax treated groups. However, no synergistic effect was observed in the p53/IL-2 combination group. Demonstrating for the first time, bax showed a significant reduction of tumor volume when compared to p53 (p < 0.02). Thus, our in vivo studies show that delivery of naked therapeutic genes is safe and results in significantly slower progression of glioma in athymic rodents.

Analysis of Variance↗

Accuracy of intravenous infusion pumps in continuous renal replacement therapies.

Most extracorporeal continuous renal replacement therapies (CRRT) require inflow pumping of either dialysate, filtrate replacement solution, or both. Outflow of spent dialysate and ultrafiltrate can be accomplished by gravity drainage or pump. Intravenous infusion pumps have been commonly used for these purposes, although little is known about the accuracy of these pumps. To evaluate accuracy of two different types of intravenous infusion pumps used in CRRT, we studied flow rates at nine different pressure variations in three piston type and three linear peristaltic pumps. The results showed that error of either pump was not different for flow rates of 4 and 16 ml/min. Both types of pumps were affected by fluid circuit pressures, although pressure conditions under which error was low were different for each pump type. The linear peristaltic pumps were most accurate under conditions of low pump inlet pressure, whereas piston pumps were most accurate under conditions of low pump pressure gradient (outlet minus inlet) of 0 or -100 mmHg. The magnitude of error outside these conditions was substantial, reaching 12.5% for the linear peristaltic pump when inlet pressure was -100 mmHg and outlet pressure was 100 mmHg. Error may be minimized in the clinical setting by choosing the pump type best suited for the pressure conditions expected for the renal replacement modality in use.

Equipment Design↗

Maximum ultrafiltration rate in continuous arteriovenous hemofiltration does not occur at the lowest level of the ultrafiltrate collection chamber.

A common assumption is that increasing transmembrane pressure by lowering the ultrafiltrate receptacle and the accompanying fluid column should always result in increasing ultrafiltration in continuous arteriovenous hemofiltration (CAVH) systems. To test this assumption, CAVH circuits were operated in vitro with use of a recirculating apparatus with an adjustable elevated reservoir. Hydraulic operational characteristics were studied in a variety of CAVH circuits, lowering the height of the ultrafiltrate column stepwise until it was at the lowest height possible. The results for most experiments performed reveal that ultrafiltration rate (UFR) reaches a peak and then declines as the collection receptacle is lowered further. There is also a decline in pre-filter blood flow preceding the peak in UFR. At lower blood flow, UFR decreases for the same transmembrane pressure (TMP). Therefore, as ultrafiltrate pressure is decreased, the effect of increased TMP on UFR is opposed by the effect of decreased blood flow, which decreases UFR. The implication of this in clinical medicine is that one may need to empirically test UFR in a CAVH system in positions other than the very lowest position.

Blood Flow Velocity↗