Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma: implications for tumor chemoresistance.

Neuroblastoma (NB) is a pediatric tumor of neural crest origin with heterogeneous phenotypes. Although low-stage tumors carry a favorable prognosis, >50% of high-risk NB relapses after treatment with a fatal outcome. Thus developing therapies targeting refractory NB remains an unsolved clinical problem. Brain-derived neurotrophic factor (BDNF) and its TrkB receptor are known to protect NB cells from chemotherapy-induced cell death, while neuropeptide Y (NPY), acting via its Y2 receptor (Y2R), is an autocrine proliferative and angiogenic factor crucial for maintaining NB tumor growth. Here we show that in NB cells, BDNF stimulates the synthesis of NPY and induces expression of another one of its receptors, Y5R. In human NB tissues, the expression of NPY and Y5R positively correlated with the expression of BDNF and TrkB. Functionally, BDNF triggered Y5R internalization in NB cells, whereas Y5R antagonist inhibited BDNF-induced p44/42 mitogen-activated protein kinase activation and its pro-survival activity. These observations suggested TrkB-Y5R transactivation that resulted in cross-talk between their signaling pathways. Additionally, NPY and Y5R were upregulated in a BDNF-independent manner in NB cells under pro-apoptotic conditions, such as serum deprivation and chemotherapy, as well as in cell lines and tissues derived from posttreatment NB tumors. Blocking Y5R in chemoresistant NB cells rich in this receptor sensitized them to chemotherapy-induced apoptosis and inhibited their growth in vivo by augmenting cell death. In summary, the NPY/Y5R axis is an inducible survival pathway activated in NB by BDNF or cellular stress. Upon such activation, Y5R augments the pro-survival effect of BDNF via its interactions with TrkB receptor and exerts an additional BDNF-independent anti-apoptotic effect, both of which contribute to NB chemoresistance. Therefore, the NPY/Y5R pathway may become a novel therapeutic target for patients with refractory NB, thus far an incurable form of this disease.

Pulse spectrum analysis of chemical factory workers with abnormal blood test.

Double blind tests to check the correlation between pulse diagnosis and liver function tests were performed. Blood tests including T-Bil, D-Bil, SGOT and SGPT of 70 chemical factory workers were compared with pulse analysis. Special attention was paid to the indicators of liver and lung meridians for pulse diagnosis. It was found that using the criterion (1) C1 > or = 3+ and C1 + C4 > or = 4+ (hyperfunction) and (2) C1 < or = 3-(hypofunction) as abnormal liver meridian (for C1, every 5% above normal give one +, every 5% below normal give one-; for C4 every 10% above normal give one +, every 10% below normal give one -). The correlation or agreement between the blood tests and the pulse diagnosis was very high (noncorrelation chance checked by X2-test, P < 0.001, degree of agreement checked by Kappa test Ka = 0.61 which means a substantial relationship). Suggestions such as more tests, more criteria and precautions for future study are also proposed.

Further analysis of a pilot study for planning an extensive clinical trial in traditional medicine--with an example of acupuncture treatment for stroke.

Statistical methods for evaluating the effects of treatments and prognostic factors in clinical trials are discussed. Exploratory data analysis, nonparametric methods, regression modeling, and regression diagnostics of influential cases are applied to the analysis of a pilot 'randomized' controlled trial on the treatment of acute stroke with acupuncture. The utility of this analysis for modifying patient eligibility criteria, determining required sample size and utilizing stratified randomization in a future extensive stroke trial is discussed.

A randomized controlled trial on the treatment for acute partial ischemic stroke with acupuncture.

The effectiveness of acupuncture in acute stroke remains largely untested and unproved. A randomized, controlled trial was carried out to study the feasibility of acupuncture in combination with conventional supportive treatment for acute stroke patients. A total of 30 patients, aged 46-74, with the onset of symptoms within 36 h were enrolled into the study after appropriate screening. All patients gave informed consent. Basing on the same supportive treatment, patients were randomly assigned to a treatment with or without acupuncture. The procedure and acupoint selection were discussed and decided through several meetings of a group of senior acupuncture doctors in Taiwan. Acupuncture was applied 3 times/week for 4 weeks. During the study period, there were no problems in conducting this trial in terms of patient availability and acceptance, and physician cooperation. A significantly better neurologic outcome was observed in the acupuncture group on day 28 and day 90. The improvement in neurologic status was greatest in patients with a poor neurologic score at baseline. There were no important side effects except for one episode of dizziness related to acupuncture treatment. The data and results of this study will be used as a guideline for planning a full-scale clinical trial, e.g. sample size calculation, method of randomization with stratification of prognostic factors, choosing acupuncture points and technique of acupuncture.

Effect of emitted bioenergy on biochemical functions of cells.

The 3-5 microns infrared spectra of the external "Qi" generated by a "Qigong" master from his palm was measured using a III-V compound semiconductor InSb detector. It was found that certain Qigong master can emit two opposite kinds of "Qi": the "facilitating" (beneficial) and "inhibiting" (destroying) "Qi". During the facilitating "Qi" emission, large amount of infrared wave were detected by a temperature rise of the air in the vicinity. When the inhibiting "Qi" was emitted, the infrared wave was absorbed from the environment resulting in a cooling of the air. The temperature rise or drop possibly reflects the fact that the blood flow to the palm was increased or decreased by dilating or constricting the blood vessels through parasympathetic or sympathetic nerves. The biochemical effects of emitted "Qi" from the same Qigong master on the human fibroblast FS-4 were investigated. The facilitating "Qi" caused 1.8% increase of the cell growth in 24 hrs, 10-15% increase of DNA synthesis and 3-5% increase of protein synthesis of the cell in a 2-hr period; while inhibiting "Qi" caused 6% decrease of cell growth in a 24 hr period, 20-23% decrease of DNA synthesis and 35-48% of protein synthesis in a 2-hr period. In addition, we found that the respiration rate of boar sperm increased 12.5-13.0% after receiving 5 min exposure in facilitating "Qi," and a decrease to 45-48% by exposure to 2-min of inhibiting "Qi." The results could be attributed to the effects of emitted "Qi" or energy containing infrared light (wave) and possibly some other types of energy.

Recent developments in clinical acupuncture.

Recent developments in the field of clinical acupuncture in the USA and worldwide are reviewed. The discovery of beta-endorphin in support of acupuncture pain relief is discussed. Other neurotransmitters in relation to the mechanism of action of acupuncture are examined. The uses of acupuncture in treating functional disorders are listed and discussed. Supporting evidence from animal experimentation is examined. The electro-acupuncture according to Voll (EAV) system is introduced as a means to standardize the therapeutic effectiveness of acupuncture. With standardization of the therapeutic effectiveness of this procedure, the author sees acupuncture as a simple, economical and effective treatment modality.

Office termination of pregnancy by "menstrual aspiration".

A program of office menstrual aspiration was initiated in our institution in 1972. Since that time 1,443 patients have been admitted into the study. These patients were evaluated by age, marital status, gravidity, repeat pregnancy terminations, complications, and detailed tissue analysis as well as contraception utilized at the time of conception and following counseling after the procedure. A majority of these patients were less than 25 years old and single; 28% had had a previous termination and 51% a previous pregnancy. Pathologic evaluations revealed Arias-Stella reaction in 78%. When these data were compared to those of a similar group of women whose pregnancies were terminated in the hospital by suction curettage, it was found that the office procedure is comparatively safe and should therefore be the therapy of choice.

A cytogenetic study of spontaneous abortions in Hawaii.

Cytogenetic results on 234 spontaneous abortions showed 109 (46.6%) to have a chromosome abnormality. The results were analysed separately for the four major ethnic groups of which the population was composed and no differences in the proportion or types of chromosome abnormalities seen. The results of this survey were found to be very similar to other major published surveys and it therefore appears, on present evidence, that neither geographic location nor racial group affects the frequency of chromosome abnormalities seen among human spontaneous abortions. The sex ratio among the chromosomally normal and abnormal abortuses and the effect of parental and gestational age were discussed.

The influence of acupuncture stimulation during pregnancy: the induction and inhibition of labor.

Uterine response to electroacupuncture stimulation of specific sites of the extremities is demonstrated in 60 pregnant women--48 cases for labor induction and 12 cases for inhibition of premature labor. In the 34 term, post-term, and 7 intrauterine fetal death cases, induction of labor was attempted; in 32 cases delivery was achieved, resulting in a success rate of 78%. In 7 cases of midterm abortion attempts, all failed to respond. Of the 12 cases of premature labor, with the exception of 1 case, all carried the pregnancy to term, resulting in a success rate of 91.6%. Based on these clinical observations, electroacupuncture may become a useful tool in controlling labor. The possible mechanism of action is discussed. Further investigation and standardization of this technique is proposed.

Hepatitis B antigen in infants born to mothers with chronic hepatitis B antigenemia in Taiwan.

Hepatitis B antigen (HB Ag) was detected by complement fixation (CF) in serum samples of 7.5% of 1,106 pregnant Chinese women tested in Taipei, Taiwan. HG Ag persisted in all but one of 42 women followed for 1 to 18 months (average, nine months) after delivery, and 27 of the 43 infants (63%) born to those women became antigen-positive. Persistance of the antigen was more common than transient or intermittent antigenemia. Twelve had antigenemia when first tested, while 15 later developed antigenemia, usually during the first six months of life. Only one infant developed antibody to HG Ag (anti-HB Ag), and this occurred after transient antigenemia. The HB Ag was found in two of 32 (6%) fathers, and in 18 of 27 (67%) older siblings. The antigen was more common among siblings of antigen-positive than among those of antigen-negative infants. These findings demonstrate that in Taiwan, infants born to mothers who are asymptomatic carriers of HB Ag commonly become infected by heaptitis B (HB) virus. Exposure of infants near the time of birth may be important maintaining the high, chronic HB Ag carrier rate in Taiwan.