Prediction of lymphatic metastasis based on gene expression profile analysis after brachytherapy for early-stage oral tongue carcinoma

BACKGROUND AND PURPOSE: The management of lymphatic metastasis of early-stage oral tongue carcinoma patients is crucial for its prognosis. The purpose of this study was to evaluate the predictive ability of lymphatic metastasis after brachytherapy (BRT) for early-stage tongue carcinoma based on gene expression profiling. PATIENTS AND METHODS: Pre-therapeutic biopsies from 39 patients with T1 or T2 tongue cancer were analyzed for gene expression signatures using Codelink Uniset Human 20K Bioarray. All patients were treated with low dose-rate BRT for their primary lesions and underwent strict follow-up under a wait-and-see policy for cervical lymphatic metastasis. Candidate genes were selected for predicting lymph-node status in the reference group by the permutation test. Predictive accuracy was further evaluated by the prediction strength (PS) scoring system using an independent validation group. RESULTS: We selected a set of 19 genes whose expression differed significantly between classes with or without lymphatic metastasis in the reference group. The lymph-node status in the validation group was predicted by the PS scoring system with an accuracy of 76%. CONCLUSIONS: Gene expression profiling using 19 genes in primary tumor tissues may allow prediction of lymphatic metastasis after BRT for early-stage oral tongue carcinoma.     

Allogeneic bone marrow transplantation from unrelated human T-cell leukemia virus-I-negative donors for adult T-cell leukemia/lymphoma: retrospective analysis of data from the Japan Marrow Donor Program.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-matched related donor has been suggested to improve the poor prognosis of adult T-cell leukemia/lymphoma (ATLL). However, the infusion of HTLV-I-infected cells from HTLV-I-positive related donors could lead to the development of donor-derived ATLL under immunosuppressive conditions. Although most ATLL patients lack a suitable HLA-matched related donor and require an HTLV-I-negative unrelated donor, little information is currently available regarding the outcome of unrelated bone marrow transplantation (UBMT) for ATLL. To evaluate the role of UBMT in treating ATLL, we retrospectively analyzed data from 33 patients with ATLL treated by UBMT through the Japan Marrow Donor Program (JMDP). Overall survival (OS), progression-free survival, and cumulative incidence of disease progression and progression-free mortality at 1 year after UBMT were 49.5%, 49.2%, 18.6%, and 32.3%, respectively. Multivariate analysis identified recipient age as an independent prognostic factor for OS (P = .044). Patients age >or=50 years who showed nonremission at transplantation tended to have higher rates of treatment-related mortality. Our observations suggest that UBMT could represent a feasible treatment option for ATLL patients and warrant further investigation based on these risk factors.     

Temporal association between sleep apnea–hypopnea and sleep bruxism events

There is some evidence suggesting that obstructive sleep apnea–hypopnea syndrome is concomitant with sleep bruxism. The aim of this study was to investigate the temporal association between sleep apnea–hypopnea events and sleep bruxism events. In an open observational study, data were gathered from 10 male subjects with confirmed obstructive sleep apnea–hypopnea syndrome and concomitant sleep bruxism. Polysomnography and audio‐video recordings were performed for 1 night in a sleep laboratory. Breathing, brain, heart and masticatory muscle activity signals were analysed to quantify sleep and sleep stage duration, and number and temporal distribution of apnea–hypopnea events and sleep bruxism events. Apnea–hypopnea events were collected within a 5‐min time window before and after sleep bruxism events, with the sleep bruxism events as the pivotal reference point. Two temporal patterns were analysed: (i) the interval between apnea–hypopnea events termination and sleep bruxism events onset, called T1; and (ii) the interval between sleep bruxism events termination and apnea–hypopnea events onset, called T2. Of the intervals between sleep bruxism events and the nearest apnea–hypopnea event, 80.5% were scored within 5 min. Most intervals were distributed within a period of <30 s, with peak at 0–10 s. The T1 interval had a mean length of 33.4 s and was significantly shorter than the T2 interval (64.0 s; P < 0.05). Significantly more sleep bruxism events were scored in association with the T1 than the T2 pattern (P < 0.05). Thus, in patients with concomitant obstructive sleep apnea–hypopnea syndrome and sleep bruxism, most sleep bruxism events occurred after sleep apnea–hypopnea events, suggesting that sleep bruxism events occurring close to sleep apnea–hypopnea events is a secondary form of sleep bruxism.     

Interferon-gamma prevents apoptosis in Epstein-Barr virus-infected natural killer cell leukemia in an autocrine fashion

The significant function of cytokines includes maintenance of cell survival as well as induction of cell differentiation and/or proliferation. We demonstrate here that interferon-gamma (IFN-gamma) plays a role for progression of Epstein-Barr virus (EBV)-infected natural killer cell leukemia (NK leukemia) through maintaining cell survival. NK leukemia cells obtained from 7 patients had clonal episomal forms of EBV, indicating that the leukemic cells were of clonal origin. Although normal NK cells constitutively expressed Bcl-2, the EBV-infected NK leukemia cells lacked endogenous Bcl-2 expression and were hypersensitive to apoptosis in vitro. The addition of IFN-gamma to the culture significantly inhibited their spontaneous apoptosis without inducing cell proliferation or upregulation of Bcl-2. The NK leukemia cells constitutively secreted IFN-gamma, and the patients' sera contained a high concentration of IFN-gamma, levels that were high enough to prevent NK leukemia cells from apoptosis. Bcl-XL was not involved in the IFN-gamma-induced NK leukemia cell survival. These data suggest that the acquisition of IFN-gamma-mediated autocrine survival signals, other than Bcl-2 or BCL-XL, might be important for the development of EBV-infected NK leukemia.     

Elucidation of the relationship of BNIP3 expression to gemcitabine chemosensitivity and prognosis

AIM: To evaluate the significance of BNIP3 in the pathogenesis of pancreatic cancer, we analyzed the relationship between the expression of BNIP3 and survival rate of the patients with pancreatic cancer, or chemosensitivities in pancreatic cancer cell lines, particularly for gemcitabine, the first-line anti-tumor drug for pancreatic cancer. METHODS: To compare the expression level of BNIP3 with the resistance to gemcitabine, eight pancreatic cancer cell lines were subjected to gemcitabine treatment and the quantitative real-time RT-PCR method was used to evaluate BNIP3 expression. Immunohistochemical analysis was also performed using 22 pancreatic cancer specimens to study relationship between BNIP3 expression and survival rate. RESULTS: Although no significantly positive association between BNIP3 mRNA level and gemcitabine chemosensitivity was observed, pancreatic cancer cell lines that were sensitive to gemcitabine treatment tended to show high levels of BNIP3 expression. The converse, an absence of BNIP3 expression, was not correlated with gemcitabine resistance. We further compared the BNIP3 expression profiles of resected primary pancreaticcancer specimens with the prognosis of the patients, and found a tendency of favorable prognosis and low BNIP3 expression. CONCLUSION: High levels of BNIP3 expression cannot be used as one of the predicting factors for gemcitabine chemosensitivity, and some yet to be known factors will have to fill the gap for the accurate prediction of pancreatic cancer chemosensitivity to gemcitabine. However, BNIP3 expression may have an impact on prediction of prognosis of patients with pancreatic cancer.     

Salivary epidermal growth factor in patients with peptic ulcer]

Recent animal studies suggest salivary epidermal growth factor (EGF) has a cytoprotective effect in the upper GI tract and is one of the important factors to promote the healing of experimental ulcer. The present study was undertaken to clarify the role of salivary EGF in peptic ulcer patients. Saliva samples were collected from 129 endoscopically normal subjects and 232 peptic ulcer patients. Salivary EGF concentration was measured by RIA. Salivary EGF output in normal subjects was 5.26 +/- 0.26 (ng/5 min) (mean +/- SE). Those in patients with gastric ulcer (GU), duodenal ulcer (DU) and gastroduodenal ulcer (GDU) were 10.74 +/- 0.15, 8.13 +/- 0.83 and 9.79 +/- 0.91. EGF output in GU and GDU patients were higher than that in normal subjects respectively. Tractable GU patients (healed within 3 months with regular regimen) had higher EGF output than intractable GU patients. Among tractable GU patients, those who had healing within 8 weeks had higher output. EGF output in patients with recurrent GU was lower than that in non-recurrent GU patients. In 10 GU patients, EGF output became higher in healing stage than in active stage. Salivary EGF may promote the healing and prevent the recurrence of human gastric ulcer.     

Effects of visual stimuli on temporal order judgments of unimanual finger stimuli

Successive tactile stimuli, delivered one to each hand, are referred to spatial representation before they are ordered in time (Yamamoto and Kitazawa in Nat Neurosci 4:759–765 2001a). In the present study, we examined if this applies even when they are delivered unilaterally to fingers of a single hand. Tactile stimuli were delivered left-to-rightward relative to the body (2nd–3rd–4th) or in reverse with stimulus onset asynchrony of 100 ms. Simultaneously with the delivery of tactile stimuli, three of nine small squares arranged in a matrix of 3 × 3 were turned on as if they appeared near the tips of the fingers. Although subjects were instructed to ignore the visual stimuli and make a forced choice between the two orders of tactile stimuli, the correct-judgment probability depended on the direction of visual stimuli. It was greater than 95% when the direction of visual stimuli matched that of the tactile stimuli, but less than 50% when they were opposite to each other. When the right hand was rotated counterclockwise on the horizontal plane (90°) so that the fingers were pointing to the left, the preferred direction of visual stimuli that yielded the peak correct judgment was also rotated, although not to the full extent. These results show that subjects cannot be basing their tactile temporal order judgment solely on a somatotopic map, but rather on a spatial map on which both visual and tactile signals converge. An erratum to this article can be found at     

Perioperative music therapy with a key-lighting keyboard system in elderly patients undergoing digestive tract surgery

BACKGROUND/AIMS: It is important to minimize the perioperative mental dysfunction of elderly patients undergoing surgery and to avoid lowering their coping skills postoperatively. Music therapy for digestive tract surgery has yet not been explored. METHODOLOGY: We evaluated perioperative music therapy using a simple key-lighting keyboard system in 37 elderly patients who underwent digestive tract surgery (Group A) compared with 13 patients who were not applied music therapy (Group B). RESULTS: On the first day after surgery there were no general hemodynamic changes after music therapy. There were no significant changes in the Philadelphia Geriatric Center morale scale and the Yesavage depression scale between the day before surgery and 7 POD in both groups. The self-assessed visual analogue health scale and the number connection test worsened significantly from 58.9+/-14.6 and 159+/-47 to 42.3+/-14.6 and 199+/-51 (p<0.05), respectively, over this time in Group B, but it did not worsen significantly in Group A. The happiness score increased significantly from 3.9+/-1.1 to 4.6+/-1.2 (P<0.05) over this time in Group A, but it did not increase significantly in Group B. CONCLUSIONS: We conclude that the music therapy with a key-lighting keyboard system in elderly patients does not change postoperative hemodynamics and helps to maintain perioperative mental functioning.     

Hepatitis G virus infection from needle-stick injuries in hospital employees

A new RNA virus, hepatitis G virus (HGV) is known to be transmissible by blood transfusion. The aim of this study was to assess whether HGV is an occupational risk to hospital employees as a result of exposure to needle-stick injuries. Among 220 cases of needle-stick injuries, 21 employees were contaminated with HGV. Initially none of the 21 recipients were HGV positive. Fourteen of the 21 recipients were followed up and further tested for HGV RNA and serum antienvelope (E2) specific antibody. None of the 21 recipients exposed to HGV developed liver function abnormalities, but one of the 14 recipients became positive for HGV RNA after the injury. Anti-E2 was negative in all recipients tested. These findings suggest a low clinical risk of occupational exposure to HGV in hospital employees. Nevertheless, HGV is transmissible by needle-stick injury.