[Successful Resection Using a Posterior Approach of a Tailgut Cyst in the Retrorectal Space].

We present the case of a Tailgut cyst occurring in the retrorectal space that was curatively resected using a posterior approach. A 40-year-old man presented to the Kochi Health Sciences Center with the chief complaint of perineal incongruity. Pelvic magnetic resonance imaging revealed a multilocular cystic lesion in the retrorectal space, with high signal intensity on T2-weighted imaging. After diagnosing a Tailgut cyst, we performed resection of the tumor using a posterior approach. The lesion was removed en bloc with the coccyx. Histopathologically, the lesion was diagnosed as a non-malignant Tailgut cyst, and the surgical margin was negative. The patient is currently doing well without recurrence at 20 months.

A Novel Potent and Selective Histamine H3 Receptor Antagonist Enerisant: In Vitro Profiles, In Vivo Receptor Occupancy, and Wake-Promoting and Procognitive Effects in Rodents.

Histamine H3 receptor antagonists/inverse agonists are known to enhance the activity of histaminergic neurons in the brain, thereby promoting arousal and cognition. Here, we report the in vitro and in vivo pharmacological profiles for a newly synthesized histamine H3 receptor antagonist/inverse agonist: [1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl](morpholin-4-yl)methanone monohydrochloride (enerisant hydrochloride). In vitro assays showed that enerisant was a competitive antagonist/inverse agonist with a high affinity and selectivity for human and rat histamine H3 receptors. Enerisant showed antagonist activity in vivo, as assessed using R-α-methylhistamine (a histamine H3 receptor agonist)-induced dipsogenia, and occupied the histamine H3 receptor in the frontal cortex in a dose-dependent manner. Enerisant also enhanced the extracellular levels of histamine in the posterior hypothalamus and the levels of dopamine and acetylcholine in the medial prefrontal cortex of rats. Enerisant exerted a procognitive effect or reversed scopolamine-induced cognitive impairment in a social recognition test and a novel object recognition test in rats at doses at which less than 50% of the histamine H3 receptor were occupied (0.03-0.3 mg/kg, p.o.). In contrast, higher doses (3-10 mg/kg, p.o.) at which nearly all the histamine H3 receptors were occupied were needed to exert wake-promoting effects in rats. These results indicate that enerisant is a potent and selective histamine H3 receptor antagonist/inverse agonist with the potential to promote arousal and procognition in rats. Moreover, the results also suggest that the histamine H3 receptor occupancy required to exert a pharmacological effect may vary depending on the domain that is being tested. SIGNIFICANCE STATEMENT: Enerisant is a novel histamine H3 receptor antagonist/inverse agonist that exerts wake-promoting and procognitive effects in addition to increasing the release of neurotransmitters related to these pharmacological effects in rodents. Moreover, an in vivo receptor binding study revealed that the in vivo occupancy of the histamine H3 receptor required to exert the pharmacological effects of enerisant varied, and such variations in required occupancy should be taken into account when performing dose selection in clinical studies.

Large 14C excursion in 5480 BC indicates an abnormal sun in the mid-Holocene.

Radiocarbon content in tree rings can be an excellent proxy of the past incoming cosmic ray intensities to Earth. Although such past cosmic ray variations have been studied by measurements of 14C contents in tree rings with ≥10-y time resolution for the Holocene, there are few annual 14C data. There is a little understanding about annual 14C variations in the past, with the exception of a few periods including the AD 774-775 14C excursion where annual measurements have been performed. Here, we report the result of 14C measurements using the bristlecone pine tree rings for the period from 5490 BC to 5411 BC with 1- to 2-y resolution, and a finding of an extraordinarily large 14C increase (20‰) from 5481 BC to 5471 BC (the 5480 BC event). The 14C increase rate of this event is much larger than that of the normal grand solar minima. We propose the possible causes of this event are an unknown phase of grand solar minimum, or a combination of successive solar proton events and a normal grand solar minimum.

Advanced liver fibrosis effects on the response to sofosbuvir-based antiviral therapies for chronic hepatitis C.

BACKGROUND: Sustained virological response (SVR) rates for the treatment of chronic hepatitis C virus (HCV)-infected patients have drastically improved with the use of direct-acting antiviral (DAA) therapies; however, a small minority of patients still fails to eradicate the virus. We analyzed factors associated with SVR in DAA therapy and the effect of age and liver fibrosis on treatment response. METHODS: Nine hundred and eighteen patients with chronic HCV infection were treated with 24 weeks of daclatasvir plus asunaprevir (DCV + ASV) or 12 weeks of sofosbuvir plus ledipasvir (SOF + LDV), ombitasvir, paritaprevir plus ritonavir (OMB + PTV + r) or sofosbuvir plus ribavirin (SOF + RBV). Multivariate logistic regression analysis was used to identify factors associated with SVR. The effect of age and liver fibrosis on SVR was analyzed. RESULTS: The overall SVR rate was 95.4% (876 of 918 patients), and rates by DAA regimen were 93.4%, 95.7%, 100%, and 95.0% in DCV + ASV-treated, SOF + LDV-treated, OMB + PTV + r-treated, and SOF + RBV-treated patients, respectively. Patients older than 75 years achieved a similar SVR rate with those aged 75 years or younger (96.4% and 94.8%, respectively). Multivariate logistic regression analysis identified absence of DAA therapy history (odds ratio [OR], 3.868 for presence; P = 0.002) and FIB-4 index of less than 3.25 (OR, 5.042 for ≥3.25; P = 0.001) as independent predictors for SVR. SVR rates were significantly lower in patients with FIB4 index of 3.25 or more compared with those with less than 3.25, especially in sofosbuvir-based therapies such as SOF + LDV-treated or SOF + RBV-treated patients. CONCLUSION: Both older and younger patients respond similarly to DAA therapy. Advanced liver fibrosis affects the virological response to sofosbuvir-based therapy.

A signature of cosmic-ray increase in AD 774-775 from tree rings in Japan.

Increases in (14)C concentrations in tree rings could be attributed to cosmic-ray events, as have increases in (10)Be and nitrate in ice cores. The record of the past 3,000 years in the IntCal09 data set, which is a time series at 5-year intervals describing the (14)C content of trees over a period of approximately 10,000 years, shows three periods during which (14)C increased at a rate greater than 3‰ over 10 years. Two of these periods have been measured at high time resolution, but neither showed increases on a timescale of about 1 year (refs 11 and 12). Here we report (14)C measurements in annual rings of Japanese cedar trees from ad 750 to ad 820 (the remaining period), with 1- and 2-year resolution. We find a rapid increase of about 12‰ in the (14)C content from ad 774 to 775, which is about 20 times larger than the change attributed to ordinary solar modulation. When averaged over 10 years, the data are consistent with the decadal IntCal (14)C data from North American and European trees. We argue that neither a solar flare nor a local supernova is likely to have been responsible.

Surgical Management in Patients with Gastrointestinal Stromal Tumors: A Single-Center Experience.

BACKGROUND: We have revisited prognostic outcomes and recurrence patterns in patients with gastrointestinal stromal tumors (GISTs) who underwent complete surgical resection at a single institution. PATIENTS AND METHODS: Patients who underwent curative surgical treatment were divided into two groups: those with high-risk GISTs (high-risk group) and those with very low-, low-, and intermediate-risk GISTs (lower-risk group). RESULTS: A total of 109 patients who underwent surgery as an initial treatment for GIST were studied. The overall 5- and 10-year survival rates after surgery were 90.3 and 71.1%, respectively. The 5-year survival rate in high-risk group patients was 88.1%, and their overall survival rate did not vary significantly from that of the lower-risk group (5-year survival rate, 91.3%). The recurrence rate in patients with high-risk GISTs gradually increased without reaching a plateau, with a cumulative rate of GIST recurrence of 26.4 and 48.9% at 5 and 10 years after surgical treatment, respectively. CONCLUSIONS: Our data suggest that the repeat surgical management in metastatic GIST is of clinical usefulness whatever the risk and improves survival.

Neoadjuvant imatinib treatment and laparoscopic anus-preserving surgery for a large gastrointestinal stromal tumor of the rectum.

BACKGROUND: Resection of a gastrointestinal stromal tumor (GIST) of the rectum can be difficult because of the particular location in the pelvis, and a large rectal GIST often requires abdominoperineal resection. Recent reports demonstrate that neoadjuvant imatinib treatment improves surgical outcomes in patients with a rectal GIST, and there are only a few reports of the effectiveness of laparoscopic surgery for a rectal GIST. CASE PRESENTATION: A 46-year-old man was found to have a rectal GIST that measured 80 mm and was located on the anterior wall of the lower rectum. After 6 months treatment with imatinib, the tumor decreased in size to 37 mm, and laparoscopic low anterior resection was performed. The patient is currently alive without any evidence of recurrence 37 months after surgery. CONCLUSIONS: Neoadjuvant imatinib should be a treatment of choice for a large rectal GIST. When marked tumor shrinkage is achieved, laparoscopic surgery may be the preferred procedure.

Rapid shrinkage of a pancreatic serous cystadenoma with cystic degeneration: report of a case.

We report a rare case of pancreatic serous cystadenoma, which shrank remarkably from 6 to 1.5 cm in diameter, with cystic degeneration, over a period of only 3 weeks. A 29-year-old woman who presented with epigastric pain and jaundice underwent computed tomography, which showed a 6-cm monolocular cystic tumor in the pancreatic head. Endoscopic retrograde cholangiopancreatography showed stenosis and deviation of the inferior part of the extrahepatic bile duct. We performed surgery 3 weeks later for suspected mucinous cystadenoma or macroscopic serous cystadenoma of the pancreas. At laparotomy, the tumor in the pancreatic head was found to have shrunk remarkably. We excised the tumor completely by performing the Whipple procedure. Macroscopically, the mass was a 1.5-cm monolocular cyst. Microscopically, the cystic tumor was composed of a thick fibrous wall with granulation tissue and hemorrhage. Although epithelial cells were not found inside the cystic wall, numerous grossly invisible microcysts with glycogen-containing epithelial cells were seen at its periphery. Based on these findings, the tumor was diagnosed as a serous cystadenoma with cystic degeneration.

Functional discrepancy between two liver lobes after hemilobe biliary drainage in patients with jaundice and bile duct cancer: an appraisal using (99m)Tc-GSA SPECT/CT fusion imaging.

PURPOSE: To determine the functional discrepancy between the two liver lobes using technetium 99m ((99m)Tc) diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ( GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ) single photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging following preoperative biliary drainage and portal vein embolization ( PVE portal vein embolization ) in patients with jaundice who have bile duct cancer ( BDC bile duct cancer ). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, with waiver of informed consent. Preoperative (99m)Tc- GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin SPECT/CT fusion images from 32 patients with extrahepatic BDC bile duct cancer were retrospectively reviewed. Patients were classified into four groups according to the extent of biliary drainage and presence of a preoperative right PVE portal vein embolization : right lobe drainage group (right drainage), bilateral lobe drainage group (bilateral drainage), left lobe drainage group (left drainage), and left lobe drainage with right PVE portal vein embolization group (left drainage with right PVE portal vein embolization ). Percentage volume and percentage function were measured in each lobe using fusion imaging. The ratio between percentage function and percentage volume (the function-to-volume ratio) was calculated for each lobe, and the results were compared among the four groups. Statistical analysis was performed with Wilcoxon signed-rank tests and Mann-Whitney U tests. RESULTS: The median values for the function-to-volume ratio in the right drainage, bilateral drainage, left drainage, and left drainage with right PVE portal vein embolization group were 1.12, 1.05, 1.02, and 0.81 in the right lobe; and 0.51, 0.88, 0.96, and 1.17 in the left lobe. Significant differences in the function-to-volume ratio were observed among the four groups (right drainage vs bilateral drainage vs left drainage vs left drainage with right PVE portal vein embolization ; with P < .002, P = .023, and P < .002 for the right lobe and P < .001, P = .023, and P < .002 for the left lobe). CONCLUSION: Hepatic lobar function significantly differs between the two lobes, depending on the extent of biliary drainage and the presence of portal vein embolization.

RSPO fusion transcripts in colorectal cancer in Japanese population.

R-spondin (RSPO) gene fusions have recently been discovered in a subset of human colorectal cancer (CRC) in the U.S. population; however, whether the fusion is recurrent in CRC arising in patients from the other demographic areas and whether it is specific for CRC remain uncertain. In this study, we examined 75 primary CRCs and 121 primary lung cancers in the Japanese population for EIF3E-RSPO2 and PTPRK-RSPO3 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of EIF3E-RSPO2 and PTPRK-RSPO3 was not detected in any of the lung carcinomas, RSPO fusions were detected in three (4%) of the 75 CRCs. Two CRCs contained EIF3E-RSPO2 fusion transcripts, and another CRC contained PTPRK-RSPO3 fusion transcripts. Interestingly, in one of the two EIF3E-RSPO2 fusion-positive CRCs, a novel fusion variant form of EIF3E-RSPO2 was identified: exon 1 of EIF3E was connected to exon 2 of RSPO2 by a 351-bp insertion. A quantitative RT-PCR analysis revealed that RSPO mRNA expression was upregulated in the three CRCs containing RSPO fusion transcripts, while it was downregulated in nearly all of the other CRCs. An immunohistochemical analysis and a mutational analysis revealed that the RSPO fusion-containing CRC had a CDX2 cell lineage, was positive for mismatch repair protein expression, and had the wild-type APC allele. Finally, the forced expression of RSPO fusion proteins were shown to endow colorectal cells with an increased growth ability. These results suggest that the expression of RSPO fusion transcripts is related to a subset of CRCs arising in the Japanese population.

Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4.

The identification of cancer biomarkers is critical for target-linked cancer therapy. The overall level of phosphatidylcholine (PC) is elevated in colorectal cancer (CRC). To investigate which species of PC is overexpressed in colorectal cancer, an imaging mass spectrometry was performed using a panel of non-neoplastic mucosal and CRC tissues. In the present study, we identified a novel biomarker, PC(16:0/16:1), in CRC using imaging mass spectrometry. Specifically, elevated levels of PC(16:0/16:1) expression were observed in the more advanced stage of CRC. Our data further showed that PC(16:0/16:1) was specifically localized in the cancer region when examined using imaging mass spectrometry. Notably, because the ratio of PC(16:0/16:1) to lyso-PC(16:0) was higher in CRC, we postulated that lyso-PC acyltransferase (LPCAT) activity is elevated in CRC. In an in vitro analysis, we showed that LPCAT4 is involved in the deregulation of PC(16:0/16:1) in CRC. In an immunohistochemical analysis, LPCAT4 was shown to be overexpressed in CRC. These data indicate the potential usefulness of PC(16:0/16:1) for the clinical diagnosis of CRC and implicate LPCAT4 in the elevated expression of PC(16:0/16:1) in CRC.

[Marked response to oral administration of UFT and leucovorin for liver metastases from colon cancer in an elderly patient].

A83 -year-old man was admitted to our hospital for the treatment of advanced ascending colon cancer with liver metastases. He had initially undergone an ileocecal resection for ascending colon cancer. Subsequently, we started oral administration of UFT/LV(UFT 400mg/day, LV 75 mg/day, and 4 weeks of therapy followed by a week suspension of treatment). After 3 courses, his tumors responded well to treatment, and CT showed marked regression of liver metastases. After 10 courses, liver metastases had almost disappeared. Two years passed without any adverse events since UFT/LV therapy was started. These findings suggest that UFT/LV therapy is very safe and effective for elderly patients with unresectable colorectal cancer.

Molecular diversity of the two sugar-binding sites of the ß-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin.

A critical role in internalizing the Clostridium botulinum neurotoxin into gastrointestinal cells is played by nontoxic components complexed with the toxin. One of the components, a ß-trefoil lectin has been known as HA33 or HA1. The HA33 from C. botulinum type A (HA33/A) has been predicted to have a single sugar-binding site, while type C HA33 (HA33/C) has two sites. Here we constructed HA33/C mutants and evaluated the binding capacities of the individual sites through mucin-assay and isothermal titration calorimetry. The mutant W176A (site I knockout) had a K(d) value of 31.5mM for galactose (Gal) and 61.3mM for N-acetylgalactosamine (GalNAc), while the K(d) value for N-acetylneuraminic acid (Neu5Ac) was too high to be determined. In contrast, the double mutant N278A/Q279A (site II knockout) had a K(d) value of 11.8mM for Neu5Ac. We also determined the crystal structures of wild-type and the F179I mutant in complex with GalNAc at site II. The results suggest that site I of HA33/C is quite unique in that it mainly recognizes Neu5Ac, and site II seems less important for the lectin specificity. The architectures and the properties of the sugar-binding sites of HA33/C and HA33/A were shown to be drastically different.

Video. Advantages of the laparoscopic approach for intersphincteric resection.

BACKGROUND: Intersphincteric resection (IRS) is a surgical technique used to preserve sphincter function, mainly cases of low rectal cancer located less than 5 cm from the anal verge [1, 2]. There have been reports of laparoscopic ISR [3, 4], but discussion of the specific techniques used in this laparoscopic surgical procedure have not been sufficient. For better outcomes of this sophisticated procedure, extreme care must taken to prevent perforation of the rectal wall and to preserve the external sphincter muscle. The most difficult steps for ISR are the circular dissection and separation of the internal sphincter muscle from the external sphincter and puborectalis using the perineal approach. The authors' techniques and the advantages of laparoscopic ISR are shown by a video presentation of three rectal tumor cases. Also, the perioperative outcomes for the patients who underwent laparoscopic ISR with this technique are described. METHODS: From January 2006 to September 2009, laparoscopic ISR with total mesorectal excision was performed for 15 patients (10 men and 5 women). The median age of the patients was 60.5 years. The T categories of the tumor node metastasis (TNM) classification for the rectal cancers were Tis for two patients, T1 for one patient, T2 for four patients, and T3 for eight patients. The median distance from the anal verge to the tumor in this series was 3.7 cm. The Tis cases had large laterally spreading tumors that could not be removed by endoscopic submucosal dissection. The T1 case presented in the video had a small tumor just above the dentate line that had developed in the presence of chronic ulcerative colitis. Because this case required total proctocolectomy and ileal pouch anal anastomosis, local resection was not used (Table 1). Table 1 Patients' clinical characteristics (2006.1-2009.8) No. of patients: 15 Gender (M/F):10/5 Age: years (range): 60.5 (31-75) pT*: Tis (n=2), T1 (n=1), T2 (n=4), T3 (n=8) Distance from anal verge: cm (range): 3.7 (2-5) * Pathological T categories of the tumor node metastagis (TNM) classification CASES: The 68-year-old man in case 1 had a large, laterally spreading rectal tumor. The 61-year-old man in case 2 had rectal cancer, with a tumor located 4 cm from the anal verge. Laparoscopic surgery was performed after neoadjuvant chemoradiotherapy. The 71-year-old woman in case 3 had T1 rectal cancer, with a tumor located just above the dentate line. After dissection of the intersphincteric space, the prolapsing technique was used. METHODS: In the male patients, the rectum with the mesorectum was first dissected to the anal hiatus, initially on the posterior side along the avascular plane. Second, Denonvilliers' fascia was dissected, and the seminal vesicle was exposed. The third step was dissection of the lateral tissues followed by incision of Denonvilliers' fascia with the rectal wall exposure and care taken not to injure the neurovascular bundle (Fig. 1). Along this dissection plane, the puborectalis could be reached and intersphincteric space entered from the lateral side of the rectal wall (Fig. 2). The final step was dissection of the hiatal ligament at the posterior side of the rectum. Nearly circular dissection of the intersphincteric space could be completed. The difficulties associated with the perineal approach were reduced by this abdominal approach, and the tumor could be exteriorized easily. Fig. 1 After incission of the Denonvilliers' fascia at the lateral side of the seminal vesicle puborectalis muscle can be reached at the lateral side of the rectum. Fig. 2 Adhesion line between the puborectalis muscle and rectal wall is enposed. Intersphinecteric space can be entered along this dissection plane at the lateral side of the rectum. RESULTS: The mean duration of surgery was 386 min, and the mean blood loss was 108 ml. The mean postoperative hospital stay was 18 days. The diverting ileostomy was closed at a mean of 7.3 postoperative months. No remarkable perioperative complication was encountered (Table 2). Table 2 Perioperative outcomes (n=15) Duration of surgery: min (range) 386 (319-510) Blood loss: ml (range) 108 (0-180) Postoperative hospital stay: days (range) 18 (11-31) COMPLICATIONS: n (range) Anastomotic leakage 1 Stricture of the anastomosis 1 Pelvic abscess 1 Postoperative period until the stoma closure (months) 7.3 (3-16) CONCLUSION: Laparoscopic ISR enabled reduction of the difficulties associated with the perineal approach. An advantage of laparoscopic ISR is the ability clearly to visualize anatomic structures in the deep pelvic cavity.

Difference in radiocarbon ages of carbonized material from the inner and outer surfaces of pottery from a wetland archaeological site.

AMS (Accelerator Mass Spectrometry) radiocarbon dates for eight potsherds from a single piece of pottery from a wetland archaeological site indicated that charred material from the inner pottery surfaces (5052 ± 12 BP; N = 5) is about 90 (14)C years older than that from the outer surfaces (4961 ± 22 BP; N = 7). We considered three possible causes of this difference: the old wood effect, reservoir effects, and diagenesis. We concluded that differences in the radiocarbon ages between materials from the inner and outer surfaces of the same pot were caused either by the freshwater reservoir effect or by diagenesis. Moreover, we found that the radiocarbon ages of carbonized material on outer surfaces (soot) of pottery from other wetland archaeological sites were the same as the ages of material on inner surfaces (charred food) of the same pot within error, suggesting absence of freshwater reservoir effect or diagenesis.

Cumulative incidence of venous thromboembolism in patients with advanced cancer in prospective observational study.

Venous thromboembolism (VTE) is frequently observed in patients with advanced cancer. The objective of this prospective observational study was to estimate, based on intensive screening, using computed tomography, lower-extremity ultrasonography, and D-dimer testing, the prevalence of VTE in patients with advanced cancer. Patients with metastatic or locally advanced cancer without anticoagulant therapy, who were planning to receive chemotherapy during 4 weeks, were eligible. Evaluations of VTE were performed at pretreatment, 12 weeks, and 24 weeks after the start of chemotherapy. Primary endpoint was cumulative incidence of VTE for 24 weeks. Secondary endpoints included incidence of VTE (pretreatment, 12 weeks, and 24 weeks after the start of chemotherapy), VTE according to primary cancer site, symptomatic VTE, pulmonary thromboembolism (PE), and treatment of VTE. We enrolled 860 patients with a median age of 68 years, including 34% female and 71% lung cancer. Cumulative incidence of VTE for 24 weeks was 22.6% (95% confidence interval: 19.8%-25.5%) (194 of 860 patients). Incidence of VTE was 11.3% pretreatment, 16.8% 12 weeks, and 14.1% 24 weeks. Symptomatic VTE was observed in 4.0% and PE in 1.0% of patients. By multivariate analysis, sex, D-dimer level, and platelet count were independent risk factors of VTE for 24 weeks. This large prospective observational study showed that cumulative incidence of VTE was high in advanced cancer patients, mainly lung cancer. Although most patients showed asymptomatic VTE, intensive screening of VTE may be considered in advanced cancer patients, especially in women with high level of D-dimer and decreased platelet count (UMIN000015243).

[Spontaneous regression of hepatocellular carcinomas].

We report a rare case of spontaneous regression (SR) of hepatocellular carcinoma (HCC). A 70-year-old man consulted us for general fatigue. Enhanced abdominal computed tomography (CT) showed two HCCs, of 5cm in the posterior segment and 8cm around the right Glissonean pedicle with tumor thrombus in the main portal trunk. He refused to undergo any treatment, but 28 months later, CT showed complete disappearance of the hilar tumor and portal tumor thrombus, and partial regression in the posterior tumor with shrinkage of the right lobe of the liver. His PIVKA-II levels decreased from 23358 to 217mAU/ml. In the present case, tumor infarction of the portal thrombus, and the administration of imidapuril hydrochloride and Hochu-ekki-to may have caused SR.

Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer.

Germline mutations in the p53 tumor suppressor gene have been identified in patients with Li-Fraumeni syndrome (LFS) and patients with Li-Fraumeni-like syndrome (LFL). However, to date, germline p53 mutations in patients not fulfilling the criteria of LFS or LFL have been reported only very rarely. In our study, a novel germline c.584T>C (p.Ile195Thr) mutation of the p53 gene was found in a 21-year-old male with a glioblastoma and colon cancer. He had no family history of cancer within second-degree relatives, and loss of the wild-type p53 allele and overexpression of p53 protein were observed in both tumors. Functional analyses revealed transactivation and growth suppressive function activities of the Thr195-type p53 to be impaired. These results suggest germline p53 mutations to possibly be responsible for a subset of young adult patient with multiple malignant tumors, even those not meeting the clinical criteria for LFS or LFL.

Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study.

The anti-hypertensive effect of GABA-rich Chlorella was studied after oral administration for 12 weeks in the subjects with high-normal blood pressure and borderline hypertension in the placebo-controlled, double-blind manner in order to investigate if GABA-rich Chlorella, a dietary supplement, is useful in control of blood pressure. Eighty subjects with Systolic blood pressure (SBP) 130-159 mmHg or diastolic blood pressure (DBP) 85-99 mmHg (40 subjects/group) took the blinded substance of GABA-rich Chlorella (20 mg as gamma-aminobutyric acid) or placebo twice daily for 12 weeks, and had follow-up observation for an additional 4 weeks. Systolic blood pressure in the subjects given GABA-rich Chlorella significantly decreased compared with placebo (p < 0.01). Diastolic blood pressure had the tendency to decrease after intake of GABA-rich Chlorella. Neither adverse events nor abnormal laboratory findings were reported throughout the study period. Reduction of SBP in the subjects with borderline hypertension was higher than those in the subjects with high-normal blood pressure. These results suggest that GABA-rich Chlorella significantly decreased high-normal blood pressure and borderline hypertension, and is a beneficial dietary supplement for prevention of the development of hypertension.