Hypermethylation associated with inactivation of the SOCS-1 gene,a JAK/STAT inhibitor,in human hepatoblastomas

We recently demonstrated inactivation in hepatocellular carcinomas (HCCs) of the gene encoding SOCS1/JAB1/SSI-1, a JAK-binding protein that regulates the JAK/STAT signal-transduction pathway. In a follow-up immunochemical investigation of expression of SOCS-1 in hepatoblastomas (HBLs), the protein was markedly reduced in half of the HBL tumors we examined. CpG-rich regions upstream of the SOCS-1 gene were hypermehylated in 7 of the 15 HBL cases. The results suggest that hypermethylation may play an important role in silencing the SOCS-1 gene, not only in adult HCCs, but also in liver tumors arising in childhood.     

Is man able to breathe once a minute for an hour?: the effect of yoga respiration on blood gases

The ventilatory response to hypercapnia and arterial blood gases during ujjai respiration of once per minute for an hour were determined in a professional hatha yogi. The results suggest that lower chemosensitivity to hypercapnia in yoga practitioners may be due to an adaptation to low arterial pH and high PaCO2 for long periods.     

Partial protective effect of inactivated Japanese encephalitis vaccine on lethal West Nile virus infection in mice

The effect of mouse brain-derived, inactivated Japanese encephalitis (JE) vaccine on West Nile virus (WNV) infection was examined using a murine model. Mice were immunized with JE vaccine twice and challenged with lethal doses of WNV. When mice were intracranially challenged with WNV, none of the immunized mice were protected. When mice were intraperitoneally challenged, the immunized mice were protected at higher immunization levels. Cross-reactive neutralizing antibodies to WNV were induced by immunization with JE vaccine; however, the levels were much lower than those to JEV. These results indicate that the currently available mouse brain-derived inactivated JE vaccine can induce partial protective immunity to WNV in mice.     

Spectrotemporal window of integration of auditory information in the human brain

The human auditory system is adapted to integrate temporally successive sounds into meaningful entities, that is, acoustic information units. Hence, sound sequences falling within the temporal window of integration should be coded holistically as unitary representations in the human auditory cortex. Although it is well established that the auditory system operates in the frequency-temporal domain, many previous studies only focused on the temporal domain of the window of integration. Therefore, in the current study we investigated the relationship between the short-term temporal integration and the frequency integration. Event-related magnetic fields in response to infrequent omission of the second tone in repetitive tone pairs composed of two closely spaced tones of different frequencies were recorded. This omission elicited the magnetic counterpart (MMNm) of the electric mismatch negativity (MMN), a change-specific component mainly generated in the auditory cortex, when the interval between the two successive tones was extremely short or when the frequency difference between the two tones was small. These findings suggest that two stimuli presented in close succession might be represented in the auditory system as a unitary integrated event. In addition, as the distance between the two successive tones decreased in the spectrotemporal dimensions, the magnitude of the MMNm increased. Behavioral data also supported these neurophysiological phenomena. This work shows the first neurophysiological evidence that the two-dimensional (spectrotemporal) window of integration, which provides important constraints for the neural processing of the acoustic environment, exists in the human brain.     

C-C chemokine receptor 2 gene polymorphism in Japanese patients with multiple sclerosis

C-C chemokine receptor 2 (CCR2) is a receptor for chemoattractant protein-1 (MCP-1) and associated with infiltrating lymphocytes in chronic active multiple sclerosis (MS) lesions. To study the role of CCR2 gene in the development of MS, we investigated the CCR2-64I polymorphism in 122 MS patients and 112 healthy controls in a Japanese population. We also analysed the influence of CCR2-64I polymorphism on the clinical course, age at disease onset, and severity. The distribution of the CCR2-64I allele was significantly different between patients and controls (p=0.0187), and the 64I/64I homozygote was significantly less common in MS than in control. Logistic analysis, adjusted for HLA-DRB1*1501-positivity, revealed negative association between the CCR2-64I and MS (p=0.0204). There were no significant associations between CCR2 polymorphism and the clinical features of MS. Our results indicate that the presence of CCR2-64I allele seems to provide protection against the development of MS.     

Ileal neobladder for urinary bladder replacement following total pelvic exenteration for rectal carcinoma

OBJECTIVE: The aim of this study was to determine the feasibility of using the ileal neobladder as a substitute for the urinary bladder following total pelvic exenteration for rectal carcinoma. PATIENTS AND METHODS: Between 1992 and 1998, we performed total pelvic exenteration with ileal neobladder in 5 men with rectal carcinoma. Four patients had primary tumors, and one had recurrent disease after low anterior resection for rectal carcinoma. Histological types were adenocarcinoma in 4 and squamous cell carcinoma in 1. Invaded organs were: the urinary bladder in 1, the urinary bladder and prostate in 2, the prostate and seminal vesicle in 1, and the prostate in 1. RESULTS: There was no operative death. In 1 patient, an ileal conduit was needed because of partial necrosis of the neobladder. Minor leakage on the dorsal wall of the neobladder occurred in 2 patients, which was successfully stopped with simple closure and a gluteus maximus fasciocutaneous flap, respectively. All except one patient with the ileal conduit could void via the urethra. Complete daytime urinary continence was achieved, but nocturnal continence was maintained with voiding once or twice per night. As the urodynamic state, the mean maximum flow rate was 20.9 ml/s (range 9.0-34.1), the mean average flow rate was 7.7 ml/s (range 3.0-11.0), and the mean voided volume was 285.5 ml (range 160-432). The mean length of follow-up was 47.8 months. One patient died of local recurrence 38 months postoperatively, and 1 died of pneumonia 10 months postoperatively. Both patients could void via the urethra until death. The other three patients are currently alive without any evidence of recurrence. CONCLUSIONS: Although total pelvic exenteration is a laborious surgical procedure, an ileal neobladder could be a good alternative to the urinary bladder enabling the patients to void via the urethra with urinary continence.     

Huge cystic lymphangioma of the pancreas: report of a case

We report herein the case of a 33-year-old woman who presented with palpable abdominal swelling found to be caused by a huge lymphangioma of the pancreas. An abdominal computed tomographic (CT) scan showed a large multilocular cystic mass with water-dense contents, which was derived from the pancreatic head. A pancreaticoduodenectomy (PD) was performed because the tumor had invaded the duodenum. The resected tumor, which was 23 × 12 × 23 cm in size with 2 l of serous fluid, was pathologically diagnosed as a cystic lymphangioma. The endothelial cells lining the internal surface of the cystic spaces were immunohistochemically positive for factor VIII-R antigen and CD31. Our review of the literature revealed 45 reports of lymphangioma of the pancreas, including this one, but to the best of our knowledge this is only the fifth case that required a PD. Nevertheless, we recommend that a complete resection be performed to reduce the risk of recurrence. Received: April 3, 2000 / Accepted: March 6, 2001     

Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 μg) was intranasally (i.n.) inoculated with influenza vaccine (10 μg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3–14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 μg) was i.n. inoculated with the vaccine (10 μg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27–50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 μg) and influenza HA vaccine (1 μg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 μg) each and diphtheria–pertussis–tetanus (DPT) vaccine (10 μg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 μg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.     

Is portal infusion chemotherapy uneffective for hepatic recurrence after resection for colorectal cancer?

Sixty-six patients with colorectal cancer were studied regarding effects of prevention of hepatic recurrence in completely performed portal infusion chemotherapy. The regimen was continuous administration of 500-875 mg/body of 5-FU for 7 days and intraportal administration of 10 mg of MMC before and after 5-FU administration. Hepatic recurrence rate was 7.6% and the five year survival rate was 83.3% in portal infusion group, and 16% and 71.3% in the control group; the difference was not significant. However, the hepatic recurrence rate in patients administered more than 4 g of 5-FU was 2.5%; there was a significant difference between the portal group and control group. The five-year survival rate for patients administered more than 4 g of 5-FU was 92.3%, which was significantly higher than at less than 4 g. Excellent effects for prevention of hepatic recurrence and prognosis were obtained in patients administered more than 4 g of 5-FU. Thus, the compliance of 5-FU in portal infusion chemotherapy is important. Also, administration of MMC is suspected to enhance the effect of portal infusion chemotherapy.     

Eosinophils are activated in middle ear mucosa and middle ear effusion of patients with intractable otitis media associated with bronchial asthma

BACKGROUND: Although patients with intractable otitis media associated with bronchial asthma have extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion, systematic histological and immunohistochemical studies have not been performed. OBJECTIVES: To clarify the pathogenesis of middle ear diseases, we carried out immunohistochemical studies on middle ear specimens, particularly focusing on the characteristics of accumulated eosinophils. METHODS: Middle ear specimens obtained from eight adult patients and from 17 controls were immunohistochemically stained using monoclonal antibodies against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of eosinophil cationic protein (ECP) in middle ear effusion samples was also measured. RESULTS: In the asthmatic patients, severe round-cell infiltration was observed in the submucosa and most of the EG1-positive cells were also EG2-positive. In the control patients, the mucosa showed a fibrotic change with a few inflammatory cells, and EG1- or EG2-positive cells were quite few. The expression of IgE was found not only on the surface of mast cells but also within the plasma cells in the asthmatic patients, and the number of IgE-positive cells was about twice as high as that of mast cells. A significantly higher concentration of ECP was noted in middle ear effusion obtained from the asthmatic patients than that from the control patients. CONCLUSION: Most of the eosinophils in the middle ear mucosa and middle ear effusion were activated, resulting in degranulation and release of ECP, and local IgE production occurs in the middle ear mucosa, indicating that the intractable inflammation is closely associated with IgE-mediated late phase response with eosinophil accumulation.