Classification of Coulombic three-body systems in hyperspherical coordinates.
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Biomedical subjects
Publications and source records attributed to Z Chen.
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Three amino acid residues (glycine-14, cysteine-135, and cysteine-218) previously speculated to be important for the structure and function of Drosophila melanogaster alcohol dehydrogenase have been investigated by using site-directed mutagenesis followed by kinetic analysis and chemical modification. Mutating glycine-14 to valine (G14V) virtually inactivates Drosophila ADH, and substitution of alanine at this position (G14A) causes a 31% decrease in activity. Thermal denaturation and kinetic and inhibition studies further demonstrate that replacing glycine-14 with either alanine or valine leads to structural changes in the NAD binding domain. These results provide direct evidence for the role played by glycine-14 in maintaining the correct conformation in the NAD binding domain. On the other hand, changing of cysteine-135, -218, or both to alanine (C135A, C218A, and C135A/C218A) causes no decrease in the catalytic activity of the enzyme, indicating that neither of the cysteinyl residues is essential for catalysis. C135A and wild-type enzyme are both inactivated by DTNB. In contrast, C218A and C135A/C218A are unaffected by DTNB treatment. DTNB modification of cysteine-218 can be prevented by the substrates NAD and 2-propanol, suggesting that cysteine-218 may be in the vicinity of the active site. Cysteine-135 which is normally insensitive to DTNB becomes accessible in the presence of 2-propanol and/or NAD, suggesting a conformational change induced by binding of these substrates.
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During 1987-1988 cytogenetic studies were performed in 30 patients with acute lymphoblastic leukemia (ALL). Of the 30 patients 15 (10 children and 5 adults) were found to have abnormal karyotypes including 8 cases (27%) of pseudodiploidy, 2 cases (7%) of hypodiploidy, one case (3%) of low-hyperdiploidy (modal number 47-50), and 4 cases (13%) of high-hyperdiploidy (modal number greater than 50). Immunological classification was performed by using monoclonal antibodies in 26 patients, and the most common immunophenotype was C-ALL. The patients with abnormal karyotypes were more likely to be NuLL-ALL (6 in 14) as compared with patients with normal karyotype (1 in 12). In our series, there was no significant difference between the patients with and without cytogenetic changes in regard of clinical findings such as FAB classification, the rate of complete remission, percentage of lymphoblasts in bone marrow cells and blood picture.
Cancer therapy with cytotoxic drugs such as cisplatin or cyclophosphamide is usually associated with violent crisis of vomiting. Recently, it was shown that 5-HT3 receptor antagonists block cisplatin-induced vomiting but the mechanisms and their sites of action remain unknown. We tested the hypothesis that these agents act on structures within the central nervous system by evaluating the effectiveness of vagal stimulation in eliciting fictive vomiting in decerebrate, paralyzed and ventilated cats before and after administration of such agents. Fictive vomiting was defined as a series of large bursts of synchronous activity in the phrenic and abdominal (expiratory) nerves (retching) followed by a burst in which the abdominal activity was prolonged (expulsion). The latency and number of these co-activations were measured before and after intravenous administration of three 5-HT3 receptor antagonists (GR 38032F (Ondansetron). Zacopride, and BRL 43694A (Granisetron]. All compounds, administered at doses of 1 and 2 mg/kg failed to block vomiting behaviour in 100% and 68% of trials, respectively. Nor did their administration affect the latency and number of co-activations. We conclude that intravenous administration of 5-HT3 receptor antagonists do not act centrally on either the brainstem neuronal network known as the "vomiting center" or related neuronal structures. Our results suggest that the anti-emetic effect of 5-HT3 receptor antagonists in cisplatin-induced vomiting is mediated peripherally rather than centrally.
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HIM1, originally designated HI98, a murine monoclonal IgM antibody raised against human mononuclear cells, has been reported at the Fourth International Leukocyte Typing Workshop (called antibody M0141) to be the only one of 157 antibodies tested that inhibited binding of interleukin 3 (IL-3) to KG-1 human acute myelogenous leukemia cells and normal human monocytes. We have carried out detailed studies of the selective effect of HIM1 on IL-3-mediated stimulation of hematopoietic progenitors. Preincubation of normal human bone marrow mononuclear cells, depleted of adherent cells and T cells, with HIM1 antibody resulted in a dose-dependent inhibition of IL-3-mediated stimulation of both erythroid burst-forming units (maximum inhibition 55%) and granulocyte/macrophage colony-forming units (maximum inhibition 49%). HIM1 antibody had no effect on growth of erythroid colony-forming units in culture. In addition, preincubation of the cells with HIM1 antibody had no deleterious effect on granulocyte/macrophage colony-stimulating factor-induced growth of either erythroid bursts or granulocyte/macrophage colonies. To be certain that the HIM1 antibody did not react directly with IL-3 itself, we attempted to use immunodepletion to remove IL-3 that had been added to our culture medium. Although we were able to remove IL-3 bioactivity by immunodepletion with anti-IL-3 antibody bound to Sepharose beads, beads with attached HIM1 did not remove IL-3 activity from the medium. Polymorphonuclear neutrophils bind high levels of HIM1, although they have very few or no detectable IL-3 receptors. Therefore, this antibody appears to recognize a cell surface antigen that is critical for optimal IL-3 binding and bioactivity but is not the actual IL-3 receptor.
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Analysis of human adenosine deaminase (ADA) gene transcription in four different cell lines indicated that a high density of RNA polymerase II complexes is present at the 5' end of the gene and that the extent of transcription elongation beyond the promoter-proximal region governs gene expression. To determine the sequence requirements for a potential transcription arrest site in the promoter-proximal region, genomic clones containing the ADA promoter, exon 1, and various lengths of intron 1 were injected into Xenopus laevis oocyte germinal vesicles. Transcription analysis indicated that nascent ADA transcripts were highly represented at the promoter-proximal region of the injected templates, suggesting that transcription arrest occurred in the oocyte transcription system. Analysis of the transcription products indicated that ADA transcription initiated at the authentic start site and that the most prominent, short ADA transcripts were 105 nucleotides in length. The 3' end of these transcripts mapped within exon 1, 10 nucleotides downstream of the translation initiation codon. Deletion analysis demonstrated that sequences within exon 1 were sufficient to specify the synthesis of the 105-nucleotide transcripts. Taken together, these data suggest that a transcription arrest mechanism operates in the promoter-proximal region of the human ADA gene and that regulation of elongation beyond this point plays a major role in regulating ADA gene expression.
Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.
Although a lot of kinds of dental adhesives have been applied recently, all of them cannot meet clinical requirement completely. This paper reports a new dental adhesive containing partial phosphate diesters developed by us. We synthesized aryl phosphorodichloridates (APDC), nine kinds of phosphate diester (PDE) adhesive monomers, sodium p-toluenesulfinate (TSS) and p-toluenesulfinic acid (TSA) accelerators, polymethyl methacrylate (PMMA) powder and the other compounds. The chemical structures of PDE adhesive monomers were confirmed by IR, 1HNMR, 31PNMR, refractive index and elementary analysis etc. The results showed that the tensile bond strength (TBS) between PDE dental adhesive and human tooth was better than others reported in China and some others reported in literature.
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A statewide survey of 624 nurses in 92 hospitals in Massachusetts indicates that recombinant tissue-type plasminogen activator and streptokinase are the most widely available thrombolytic agents. Nurses play an active role in drug reconstitution and administration, but only 20% of the total respondents participate consistently in screening procedures. The majority of patients were informed about the risks and benefits of treatment before initiation of therapy. Nurses reported their major management concern was internal bleeding, with cost of treatment being a minor concern.
The present study was designed to investigate the relationship between the precruciate cortex (PreCtx) and the ventral lateral posterior nucleus (VPL) of the thalamus in the mechanisms of acupuncture analgesia. Neuronal responses in the nucleus VPL to electrical noxious stimulation of the superficial peroneal nerve were extracellularly recorded. Lidocaine was topically applied at PreCtx. Twenty minutes after the application electroacupuncture (EA) was employed at "Zusanli" and "Huantiao" points for 5 minutes. The nociceptive responses were recorded immediately after cessation of EA and consecutively recorded at the interval of 2 minutes. Similar procedures were made in the control group, in which 0.9% Nacl was topically applied at PreCtx. It was found that topical application of lidocaine at PreCtx did not influence the nociceptive responses of VPL neurons. Following topical application of lidocaine at PreCtx, the nociceptive responses were obviously inhibited 0', 4', 6', 10', and 12' after cessation of EA. In the saline control group the remarkable inhibitory effect of EA was observed 0'-8' after ceasing EA, The results showed that the inhibitory effect of EA in the test group was weaker than that in the control group. However, the difference was not statistically significant. It is suggested that PreCtx participates in the corticofugal modulation of EA effects in the nucleus VPL only to small extent.
We have previously demonstrated that during acute arthritis in the rats induced by local intraplanter adjuvant, there are dramatic alterations in the behavioral responses to noxious stimulation. The purpose of this study was to observe the changes in responses of parafascicular nuclei (Pf) neurons during acute arthritis and effect of acupuncture (EA) in the rats. It was shown that: (1). for the whole populations of somatosensory neurons there was no statistical significant between arthritic rat and normal rat (P greater than 0.05). However, nociceptive neurons activated exclusively by noxious stimulation were less in the arthritic rat (21/60) than in the normal rat (35/46) (P less than 0.01); nociceptive-non-nociceptive neurons activated by both noxious and non-noxious stimulation were more in the arthritic rat (30/60) than in the normal rat (9/46) (P less than 0.01), and there was no statistical significant different for population of non-nociceptive neurons between two groups. (2). Nociceptive responses of Pf neurons (n = 16) could be markedly inhibited by EA at Xuanzhong (G39) and Kunlun (B60) in acute arthritic rat. In particular, the inhibitory effect was of great significance (P less than 0.01) during 0-10 and 20-35 minutes following cessation of EA. These results suggest that rats were hyperalgesic during adjuvant-induced acute arthritis and EA produces a fine analgesic effect in acute arthritic rats. The results also support the view that adjuvant-induced acute arthritic rat can be considered as a model for research of pain and analgesia.