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Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 451 records · Page 25Linked to original sources

Mechanisms of antitumor activity of aqueous extracts from Chinese herbs: their immunopharmacological properties.

Previously we reported the antitumor activity of 4 kinds of Chinese herbs: A. capillaris, S. doederleinii, A. macrocephala and S. subprostrata. Evidence has been also presented that A. capillaris shows the activity mainly through a direct tumoricidal action and the others display the activity through the enhancement of tumor-immune response. The present results are as follows: A. capillaris did not affect Meth A tumor-neutralizing activity (Winn's assay) in spleen cells of BALB/c mice bearing the primary tumor. The other herbs enhanced the activity on days 10 and 15 and prevented the decay of the activity on day 20 after the Meth A tumor transplantation. However, none of them enhanced the local graft versus host reaction (GvHR) induced in CBF1 mice by spleen cells of BALB/c mice. A. capillaris hardly affected the humoral antibody formation against sheep red blood cells in mice. On the contrary, the other 3 herbs enhanced the formation. Blast transformation of murine lymphocytes with PHA-P or LPS was suppressed by 10(-5) to 10(-4) g/ml of A. capillaris. A. macrocephala enhanced the response by LPS. It should be noted that A. capillaris showed no immunosuppressive action in spite of having a direct tumoricidal action in vitro. Further investigations will be required on the latter 3 herbs to clarify the relationship between their humoral immunity-stimulating activity and their tumor immunity-enhancing activity.

Animals↗

Organization of the spinocervicothalamic pathway in the rat.

We used silver degeneration techniques to examine the termination of the spinocervical and cervicothalamic tracts in rats. Lesions of the dorsal portion of the lateral funiculus (DLF) of the spinal cord produced degeneration of a relatively small number of ascending fibers that were seen within the most lateral portion of the DLF rostral to the lesion. Within the lateral cervical nucleus, the degeneration was more extensive mediolaterally and of a finer caliber. Such labeling is attributable to the degeneration of fine fibers and terminals. Degenerating processes could be seen in apposition to neurons in the lateral cervical nucleus. At all levels of the cord, the lateral spinal nucleus was devoid of terminal labeling following lesions of the DLF. No terminal degeneration could be seen within the DLF at levels rostral to the lateral cervical nucleus. Lesions of the DLF at either midcervical or lower thoracic levels produced degeneration throughout the lateral cervical nucleus. This finding suggests that the lateral cervical nucleus of the rat is not somatotopically organized. Lesions of the lateral cervical nucleus produced degeneration of a small number of fibers within the contralateral midbrain and thalamus. Within the mesencephalon, degenerating fibers and terminals were seen primarily in the intercollicular region and the deep layers of the superior colliculus. Less degeneration was found in the lateral portion of the central gray. Within the diencephalon, a small area of termination was located in the ventromedial part of the rostral portion of the medial geniculate nucleus. A prominent termination was present in a restricted area within the caudal fourth of the ventrobasal complex.

Afferent Pathways↗

Routes of entry into the cerebellum of spinocerebellar axons from the lower part of the spinal cord. An experimental anatomical study in the cat.

Among the newly discovered spinocerebellar cell groups, those at lumbar and more caudal levels of the cat's spinal cord were studied with regard to which of the two cerebellar peduncles, the restiform body or the superior cerebellar peduncle, is used by their axons. Bilateral injections with horseradish peroxidase were made into either of the anterior lobe or the posterior cerebellar termination area for spinocerebellar fibers, following unilateral transections of either the superior cerebellar peduncle or the restiform body, combined with low contralateral transections of the lateral and ventral funiculi. Following transection of the superior cerebellar peduncle, labeled neurons were found ipsilateral to the transection in the column of Clarke and in laminae IV-VI at L 3-L 7. Contralaterally, labeled neurons were found in the ventromedial nucleus and lamina VIII of the ventral horn in the sacro-coccygeal segments and in the medial part of lamina VII at L 6 and more caudal levels. All these neurons were regarded as sending their axons through the restiform body. Following transection of the restiform body, labeled neurons were found in the following areas contralateral to the transection: the dorsolateral nucleus of the L 3-L 6 segments, the lateral part of lamina VII at L 3-L 5/6, the medial part of lamina VII in L 6 and more caudal segments, and the ventrolateral nucleus of L 4-L 5. Ipsilaterally, labeled neurons were found in lamina VIII at L 4-L 6. All these neurons were regarded as sending their axons through the superior cerebellar peduncle. In addition to new information about the peduncular routes of spinocerebellar neurons, the study has given confirming evidence as to the crossing conditions for different spinocerebellar cell groups. The findings should be useful in future studies on the organization of the spinocerebellar systems.

Afferent Pathways↗

Collateral projections of neurons from the lower part of the spinal cord to anterior and posterior cerebellar termination areas. A retrograde fluorescent double labeling study in the cat.

The collateral projections of spinocerebellar neurons located in the L 2 to Ca 1 spinal segments in the cat were investigated by retrograde fluorescent double labeling technique. Rhodamine labeled latex microspheres (Rm) and Fast Blue (FB) were used for injections into the cerebellum in 8 cats. Two additional cats, with injections of Fluoro-Gold (FG) combined with Rm were excluded because lipofuchsin autofluorescence obscured the labeling. After injections with one tracer unilaterally in the paramedian lobule and another tracer bilaterally in the anterior lobe, double labeled neurons were found on the side of the paramedian lobule injection in the column of Clarke at L 2-L 4, laminae IV-VI at L 2-L 5 and the dorsolateral nucleus at L 2-L 6. After bilateral injections of one tracer in lobule VIII B and another in the anterior lobe, double labeled neurons were found bilaterally in the column of Clarke at L 2-L 4, laminae IV-VI at L 2-L 5, the medial part of lamina VII at L 6-L 7 and in certain cell groups at sacro-coccygeal levels. Neurons in the lateral part of lamina VII at L 3-L 5 and the ventrolateral nucleus of L 4-L 5 were labeled exclusively from injections in the anterior lobe. The findings indicate that spinocerebellar neurons at lumbar and more caudal levels of the cat spinal cord have different projection patterns in the cerebellum. A certain number of neurons which project to the anterior lobe have divergent axon collaterals supplying also the posterior vermis and/or the paramedian lobule. Other neurons project to the anterior or to the posterior lobe only.

Afferent Pathways↗

Do certain spinocerebellar neurons in lamina IX at lumbosacral levels send collaterals to peripheral nerves? A retrograde fluorescent double labeling study in the cat.

Spinocerebellar neurons have been found in previous studies in lamina IX of the lumbosacral spinal cord. This lamina has been characterized as being composed of motor cell groups and the spinocerebellar neurons in the lamina have been found to have certain morphological similarities with the motoneurons. Retrograde double labeling technique, utilizing fluorescent dyes, was used for studying the relations between the spinocerebellar neurons and the motoneurons in lamina IX of the lumbosacral spinal cord in four adult cats. In three of them, Rhodamine labeled latex microspheres were injected bilaterally into the cerebellum and Fast Blue (FB) was injected into hindlimb nerves. In the fourth case, FB was injected into the cerebellum, while the peripheral nerves were injected with propidium iodide. Some overlap was found between labeled spinocerebellar neurons and motoneurons in certain parts of lamina IX, especially in the ventrolateral nucleus in the caudal part of L5 and rostral L6, in the dorsolateral nucleus from the caudal part of L5 to L6 and in the ventromedial nucleus at the S2 level. No double labeled neurons were found, however, in any of these or in other examined areas. This strongly indicates that spinocerebellar neurons in lamina IX are a separate population, different from motoneurons.

Amidines↗

Effect of immunostimulants and antitumor agents on tumor necrosis factor (TNF) production.

OK-432, a lyophilized preparation of Streptococcus pyogenes, showed a priming activity for TNF production in mice, associated with an increase of spleen weight. PSK, a protein-bound polysaccharide preparation from Coriolus versicolor, did not show such activity. Both OK-432 and PSK potentiated the TNF production in mice primed with Corynebacterium parvum (CP) and challenged with Escherichia coli endotoxin (LPS). Cytotoxic antitumor agents of 5-fluorouracil (5-FU), cyclophosphamide (CY) and bleomycin (BLM) suppressed TNF production in mice primed with CP and challenged with LPS. TNF production suppressed by 5-FU, CY and BLM was partially restored by the combined treatment with OK-432 or PSK. These results suggest that the administration of cytotoxic antitumor agents suppresses the intrinsic TNF production in cancer patients, and the combined use of immunostimulants such as OK-432 and PSK is advantageous in restoring TNF production suppressed by cytotoxic antitumor agents.

Adjuvants, Immunologic↗

The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord.

A laminar cytoarchitectonic scheme of the lower thoracic and lumbosacral segments of the rat spinal cord is presented in which Rexed's principles for the cat are applied. The material consists of 80-micron-thick sections stained with toluidine blue or according to van Gieson and 2-micron-thick sections stained with p-phenylenediamine or toluidine blue. The cytoarchitectonic organization of the rat spinal cord was found to be basically similar to that of the cat, although certain differences exist--for example, in the extension of the laminae. In addition to the laminar scheme, the distribution of certain cell groups, Lissauer's tract, and the pyramidal tract were investigated.

Animals↗

Studies on RNA ligase activity in the brain and liver cells of mouse.

RNA ligase in eukaryotic mammalian cells was studied by using mouse brain and liver cell extracts as enzyme sources and Oligo A as substrates. RNA ligase activity was determined by measuring the formation of alkaline phosphate-resistant product from 5'-32P-terminated Oligoribonucleotides. Under appropriate conditions, the activity of this enzyme in brain and liver cells may vary between 16-49 mU/ml. The joining way between donor and acceptor is 5'-P----3'-OH. Further studies were carried out by using synthetic UpCpU and 32pNp as substrates and crude enzyme preparations from extracts of cell nuclei of brain and liver as enzyme sources. RNA ligase activity was examined by homochromatography and autoradiography. A clear joining product was demonstrated and then isolated from the reaction mixture by DEAE-Sephadex A25 column chromatography. The eluted fractions were identified by DEAE-cellulose thin layer chromatography. The joining product was hydrolyzed either with KOH or with alkaline phosphatase, the autoradiographic spot of the product disappeared. In this case the joining way between donor and acceptor is 3'-P----5'-OH instead of 5'P----3'-OH. All this indicated that in extracts of mouse brain and liver cells most probably exists some other kind of RNA ligase, which differs from the T4 RNA ligase in the joining way.

Adenosine Triphosphate↗

Physical and chemical stability of gemcitabine hydrochloride solutions.

OBJECTIVE: To evaluate the physical and chemical stability of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) solutions in a variety of solution concentrations, packaging, and storage conditions. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test conditions included (1) reconstituted gemcitabine at a concentration of 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride or sterile water for injection in the original 200 mg and 1 gram vials; (2) reconstituted gemcitabine 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride injection packaged in plastic syringes; (3) diluted gemcitabine at concentrations of 0.1 and 10 mg/mL as the hydrochloride salt in polyvinyl chloride (PVC) minibags of 0.9% sodium chloride injection and 5% dextrose injection; and (4) gemcitabine 0.1, 10, and 38 mg/mL as the hydrochloride salt in 5% dextrose in water and 0.9% sodium chloride injection as simulated ambulatory infusions at 32 degrees C. Test samples of gemcitabine hydrochloride were prepared in the concentrations, solutions, and packaging required. MAIN OUTCOME MEASURES: Physical and chemical stability based on drug concentrations initially and after 1, 3, and 7 days of storage at 32 degrees C and after 1, 7, 14, 21, and 35 days of storage at 4 degrees C and 23 degrees C. RESULTS: The reconstituted solutions at a gemcitabine concentration of 38 mg/mL as the hydrochloride salt in the original vials occasionally exhibited large crystal formation when stored at 4 degrees C for 14 days or more. These crystals did not redissolve upon warming to room temperature. All other samples were physically stable throughout the study. Little or no change in particulate burden or the presence of haze were found. Gemcitabine as the hydrochloride salt in the solutions tested was found to be chemically stable at all concentrations and temperatures tested that did not exhibit crystallization. Little or no loss of gemcitabine occurred in any of the samples throughout the entire study period. However, refrigerated vials that developed crystals also exhibited losses of 20% to 35% in gemcitabine content. Exposure to or protection from light did not alter the stability of gemcitabine as the hydrochloride salt in the solutions tested. CONCLUSION: Reconstituted gemcitabine as the hydrochloride salt in the original vials is chemically stable at room temperature for 35 days but may develop crystals when stored at 4 degrees C. The crystals do not redissolve upon warming. Gemcitabine prepared as intravenous admixtures of 0.1 and 10 mg/mL as the hydrochloride salt in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as a solution of 38 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes is physically and chemically stable for at least 35 days at 4 degrees C and 23 degrees C. Gemcitabine as the hydrochloride salt is stable for at least 7 days at concentrations of 0.1, 10, and 38 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection stored at 32 degrees C during simulated ambulatory infusion.

Antimetabolites, Antineoplastic↗

Breast cancer resistance protein-mediated topotecan resistance in ovarian cancer cells.

Overexpression of breast cancer resistance protein (BCRP) and mitoxantrone (MX) resistance protein can confer resistance to a variety of cytostatic drugs, such as MX, topotecan (TPT), doxorubicin, and daunorubicin. This study investigates the role of BCRP in resistance of ovarian cancer to TPT treatment. We have developed TPT-resistant human ovarian cancer cell line. Intracellular concentration of fluorescent dye rhodamine 123 (Rh123) was measured by flow cytometry. The expression of several membrane transporter proteins including P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and BCRP were determined by reverse transcription-polymerase chain reaction and Western blotting. The Rh123 concentration in parental cells was approximately three times of those in TPT-resistant cells. In contrast to undetectable level of P-gp messenger RNA (mRNA) and minimal level of MRP1 expression in TPT-resistant cells, overexpression of both the BCRP mRNA and the protein was detected in these cells. Introduction of antisense-phosphorothioate oligonucleotide derived from BCRP mRNA into TPT-resistant cells resulted in a significant increase in the concentration of intracellular Rh123. These results suggested a novel mechanism in which a reduced intracellular drug concentration may be mediated by BCRP gene products in human ovarian cancer cells.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis.

Investigations in rabbits and humans have provided experimental evidence that autoimmune reactions play a major role in the initial stages of the development of atherosclerosis. These involve the infiltration of the arterial intima with T cells reacting with heat shock protein (hsp) 65/60 and the occurrence of anti-hsp 65/60 antibodies. This early immunologically mediated stage of atherosclerosis is still reversible but if additional risk factors, such as high cholesterol levels, come into effect, severe mostly irreversible lesions develop.

Animals↗