Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection.

Public health concern about dengue diseases, caused by mosquito-borne infections with four serotypes of dengue virus (DENV-1-DENV-4), is escalating in tropical and subtropical countries. Most of the severe dengue cases occur in patients experiencing a secondary infection with a serotype that is different from the first infection. This is believed to be due to antibody-dependent enhancement (ADE), by which one DENV serotype uses pre-existing anti-DENV antibodies elicited in the primary infection to facilitate entry of a different DENV serotype into the Fc receptor-positive macrophages. Recently, we prepared a number of hybridomas producing human monoclonal antibodies (HuMAbs) by using peripheral blood lymphocytes from Thai patients at acute phase of secondary infection with DENV-2. Here, we characterized 17 HuMAbs prepared from two patients with dengue fever (DF) and one patient with dengue hemorrhagic fever (DHF) that were selected as antibodies recognizing viral envelope protein and showing higher neutralization activity to all serotypes. In vivo evaluation using suckling mice revealed near perfect activity to prevent mouse lethality following intracerebral DENV-2 inoculation. In a THP-1 cell assay, these HuMAbs showed ADE activities against DENV-2 at similar levels between HuMAbs derived from DF and DHF patients. However, the F(ab')2 fragment of the HuMAb showed a similar virus neutralization activity as original, with no ADE activity. Thus, these HuMAbs could be one of the therapeutic candidates against DENV infection.

Umbilical diagnosis as a non-invasive visual diagnostic aide.

Using Bi-Digital O-Ring Test (Omura, Y. 1977-2002; BDORT), we have researched the abnormal shapes of the umbilicus and the surrounding areas of the umbilicus, and the relationship between diseased internal organs and abnormal shape and direction of the radial sulcus of the umbilicus for several years. In this report we have mapped the organ representation area of the umbilicus and its surrounding areas of a healthy person by using BDORT. Then the abnormal organs around the umbilicus of the patients with certain diseases were mapped by using BDORT. Also Oncogene C-fos Ab2 positive response network (specially relation between the radial sulcus and the disease) of the cancer response (Oncogene C-fos Ab2) positive person were examined all over the body. In many cases, the radial sulcus from the umbilicus and the organ representation area of abnormal organs at the umbilicus of diseased person mapped using BDORT were highly correlated. Abnormality observed in a specific organ with strong resonance by BDORT meridian network was connected to the umbilicus. Mapped chart of the organ representation area surrounding the umbilicus is clinically very useful for non-invasive visual umbilical diagnosis.

Long-lasting effect of transcutaneous electrical nerve stimulation on the thermal hyperalgesia in the rat model of peripheral neuropathy.

We demonstrate here unexpectedly long-lasting effect of transcutaneous electrical nerve stimulation (TENS) to alleviate thermal hyperalgesia in rats with peripheral neuropathy produced by constriction of sciatic nerve. For TENS groups, electrical stimulation for 16.7 min (1 Hz, paired current, 12 mA, 5-ms interval, 0.2-ms duration, 999 pairs), once a day, was delivered for 5 consecutive days, under halothane anesthesia (Hal-TENS group) or pentobarbital anesthesia (Pent-TENS group). For non-TENS groups, only the anesthesia was delivered (Hal-no TENS group, Pent-no TENS group). For the control group, neither anesthetics nor TENS was delivered. To evaluate hyperalgesia, paw withdrawal latency (PWL) to radiant heat was measured before nerve constriction and five times after the constriction; just before TENS and at 1, 3, 7, and 14 days after the completion of TENS. Compared to the non-TENS groups, rats in the TENS groups showed significantly reduced thermal hyperalgesia at least for 3 days (Pent-TENS group) or for 7 days (Hal-TENS group) after TENS. These results indicate a possible long-lasting therapeutic effect of TENS applied under general anesthesia.