Yakushi Buddha (Buddha of Healing) and its medicinal container in Japan.
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Biomedical subjects
Publications and source records attributed to J Okuda.
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Prospective memory is a memory feature in humans which involves activities for remembering to do something in the future. The present study provides functional neuroanatomy of prospective memory for the first time. We used positron emission tomography (PET) and found several localized brain activations in relation to a prospective memory task required to retain and remember a planned action while performing an ongoing routine activity. Activations were identified in the right dorsolateral and ventrolateral prefrontal cortices, the left frontal pole and anterior cingulate gyrus, the left parahippocampal gyrus, and midline medial frontal lobe. We attributed these activations to several cognitive processes involved in prospective memory, such as holding an intention toward future behavior, checking target items within presented stimuli, and dividing attention between the planned action and the routine activity.
Escherichia coli strains isolated from patients with diarrhea or hemolytic uremic syndrome (HUS) at Pusan University Hospital, South Korea, between 1990 and 1996 were examined for traits of the O157:H7 serogroup. One strain isolated from a patient with HUS belonged to the O157:H7 serotype, possessed a 60-MDa plasmid, the eae gene, and ability to produce Shiga toxin 1 but not Shiga toxin 2. Arbitrarily primed PCR analysis suggested that this strain is genetically very close to a O157:H7 strain isolated in Japan.
PURPOSE: Traumatic manipulation of cancer specimens during laparoscopic colectomy may increase exfoliation of malignant cells into the peritoneal cavity, causing an early occurrence of peritoneal carcinomatosis or port-sites recurrence. Because of this concern, the routine use of intraperitoneal chemotherapy after laparoscopic colectomy for cancer was suggested recently. We assessed if laparoscopic vs. conventional surgery increases exfoliated malignant cells in the peritoneal cavity during resection of colorectal cancer. METHODS: In a prospective, randomized fashion, 38 colorectal cancer patients undergoing an elective, curative operation were assigned to either a conventional or laparoscopic procedure between June 1996 and May 1997. In either group (n = 19), after the abdominal cavity was entered, saline was instilled into the peritoneal cavity, and the fluid was collected (Specimen 1). During surgery, all irrigating fluids were collected (Specimen 2). Both specimens were assessed for malignancy using four techniques: filtration process (ThinPrep), smear, cell block, and immunochemistry using Ber-EP4. The change in the amount of tumor cells in both specimens was compared between surgical groups. A pilot study was performed to validate the proposed cytologic method. RESULTS: In the pilot study of 20 consecutive patients with colorectal cancer, postresectional peritoneal cytology was positive in six patients, including two Stage II (T3, N0, M0) patients. The pilot study also validated that our semiquantitative scoring system can be reliably used to assess the amount of free peritoneal cancer cells. In the main study, 16 right colectomies, 3 extended right colectomies, 17 proctosigmoidectomies, and 1 left colectomy were performed. The T and N stages were T1 (n = 13, T2 (n = 5), T3 (n = 8), T4 (n = 11); N0 (n =22), N1 (n = 8), N2 (n = 7). Malignant cells were not detected in any Specimens 1 or, more importantly, in Specimens 2 in either surgical group. CONCLUSION: When performed according to strict oncologic surgical principles, laparoscopic techniques in curative colorectal cancer surgery did not have an increased risk of intraperitoneal cancer cell spillage, compared with conventional techniques. We hope that these results can decrease some of the concerns about tumor cell spillage and seeding during laparoscopy.
Thermostable direct haemolysin of Vibrio parahaemolyticus has been shown to be a major virulence factor. The Kanagawa phenomenon (KP), haemolysis induced by this haemolysin on a special blood agar medium, is strongly associated with clinical strains. We have been studying the expressions of various tdh genes encoding this haemolysin to elucidate the significance of the tdh genes possessed by KP-negative strains isolated from patients. We examined the importance of the promoter sequence variation for expression level of the tdh gene in this study. Only the tdh2 gene, one of the two tdh genes (tdh1 and tdh2) present in a KP-positive strain, was previously shown to be responsible for the haemolytic activity of the KP-positive strain. The tdh1- and tdh2-lacZ fusions were used to determine and analyse the promoter sequence by primer extension and site-directed mutagenesis methods. Two bases (positions -24 and -34) within the determined tdh2 promoter sequence were shown to be mostly responsible for the difference in the promoter strength between the tdh2 and tdh1 genes both in Escherichia coli and in V. parahaemolyticus backgrounds. Representative tdh promoters of KP-negative strains are close to the tdh2 promoter; they differ at position -34 but have the same base at position -24 as the tdh2 promoter. We demonstrated that base substitution of the tdh promoters of KP-negative strains only at position -34 is sufficient to increase the expression of these genes to the KP-positive level. Therefore, the tdh genes of KP-negative strains are considered to be potentially important because they can generate a KP-positive subclone by a point mutation in their promoters.
Twelve strains of Escherichia coli O157:H7 were isolated from 9 of 25 beef samples purchased from retail stores in Malaysia. These strains produced Shiga toxin 2 with or without Shiga toxin 1 and had the eae gene and a 60-MDa plasmid. The antibiograms and the profiles of the arbitrarily primed PCR of the strains were diverse, suggesting that the strains may have originated from diverse sources.
The purpose of this study was to develop, implement, and assess an estimation procedure for preventing drug-induced liver disorders. We have built a database for CARPIS (case reports of adverse drug reaction and poisoning information services) since 1987, and the case reports of adverse drug reaction accumulated in the CARPIS database to be total about 11,000. We studied the estimation procedure by evaluating the subjective symptoms, backgrounds and laboratory data of patients in 199 cases cumulated in the CARPIS database. The evaluation scores were created on the basis of the subjective symptoms and backgrounds of the patients. Then, we re-estimated 199 cases with the evaluation scores, among which were 165 cases (82.9%) in 199 cases drug-induced liver disorders. For the rest of 34 cases (17.1%) drug-induced liver disorders could not be estimated from our evaluation scores. These 34 cases were either those which the subjective symptoms were not described in their reports, because the patients were hospitalized for other diseases and drug-induced liver disorders were discovered by a clinical examination, or cases of infants for whom it was difficult to confirm the subjective symptoms. The validity of this evaluation scores were sensitivity = 82.9%, specificity = 91.0% and predictive value of positive test = 94.8%. To apply this evaluation scores onto the clinical practice, we prepared an evaluation form for the subjective symptoms and backgrounds of the patients with drug suspecting-induced liver disorders.
Auditory evoked magnetic fields for pure-tone stimuli were measured in seven subjects with right hemisphere dominance for language using a whole-head magnetoencephalography system linked to magnetic resonance imaging. N100m responses were observed in both hemispheres in five subjects. The N100m response latency to contralateral stimulation was significantly shorter on the right than on the left in all cases. Normal right-handed subjects with left hemisphere dominance showed exactly the same responses. Therefore, the shorter N100m latency in the right hemisphere is independent of the dominant hemisphere for language.
We examined the role of the parahippocampal regions in humans during two types of verbal recognition process, i.e. delayed matching and non-matching, by measuring regional cerebral blood flow (rCBF) using PET. The results showed differential activation of each parahippocampal region during verbal memory tasks in which the side activated shifted depending on the nature of the task employed; an increase in rCBF in the left parahippocampal gyrus was associated with retrieval strategy of non-matching, and an increase in rCBF in the right parahippocampal gyrus was associated with retrieval strategy of matching. We conclude that lateralized parahippocampal activation may depend on the type of response required.
We previously reported that treatment of human erythrocytes with bee venom phospholipase A2 increased the rate of lactate production from glucose. This increase was suggested to be mediated through liberation of free fatty acids from membrane phospholipids. So, in the present study we examined the mechanism of stimulation of glycolysis by fatty acids. Treatment of intact erythrocytes with most of the 15 fatty acids tested resulted in stimulation of lactate production from glucose. Among the fatty acids tested, myristoleic acid showed the highest stimulatory activity. The ratio of moles of lactate produced to those of glucose utilized was about 1.9 in both myristoleic acid-treated and untreated cells. Treatment of erythrocytes with myristoleic acid did not affect the amount of 2,3-bisphosphoglycerate. Lactate production from D-glyceraldehyde, which is thought to be phosphorylated to D-glyceraldehyde 3-phosphate and then metabolized in the glycolytic pathway, was not at all affected by treatment of cells with myristoleic acid. The cross-over plot of glycolytic intermediates suggested that the enhancement of glycolysis was induced by activation of the 6-phosphofructokinase (PFK) step. Fatty acids incorporated into erythrocytes were found to be present predominantly in the cytoplasm rather than in the plasma membrane. The PFK activity, but not the hexokinase activity, in hemolysates was clearly increased by a set of fatty acids, and myristoleic acid was again the most potent. However, partially purified human erythrocyte PFK was not activated by the acid. We conclude that fatty acids stimulate glycolysis through activation of PFK in cooperation with some other component(s) in erythrocytes.
In laparoscopic colorectal surgery, effective handling of the bowel is mandatory to avoid bowel injury and excessive manipulation and to obtain adequate traction and clear exposure. We have developed a simple laparoscopic tool that permits effective and safe retraction of the small or large intestine and that is especially helpful in taking down the hepatic and splenic flexures and in dissecting the mesorectum.
BACKGROUND: Because of the inability to palpate colonic tumors during laparoscopy, their location must be precisely identified before resection is undertaken. METHOD: A retrospective study was performed of 58 patients in order to be able to describe our methods of tumor localization for laparoscopic colorectal operations and to review their effectiveness. RESULTS: In all patients, the entire colon was examined preoperatively by colonoscopy. In one patient, preoperative colonoscopic localization was inaccurate. In 31 patients, tumors were easily detectable at surgery. In five patients with the tumor in the right colon, even though the lesion was not detectable at surgery, right colectomy was performed without marking because preoperative colonoscopy reliably identified the lesion adjacent to the ileocecal valve. Twenty-two patients required some type of procedure to localize the tumor. The procedures and their problems were as follows: preoperative tattoo (five)--tattoo not visualized (one); intraoperative colonoscopy alone (six), combined with intraoperative tattoo (four) or clip (three)--poor operative exposure due to bowel distension (nine), hard to see the clip (three), dislodged clip (two), inadequate resection margin (one); intraoperative proctoscopy alone (two), combined with laparoscopic stitch (two)--no problems. In no patient was tumor present at a resection line and in no patient was the wrong segment resected. CONCLUSIONS: Reliable preoperative identification of the tumor adjacent to the ileocecal valve can permit right colectomy without marking. Lesions in the upper rectum can be approached via intraoperative proctoscopy +/- suture placement. If the surgeon anticipates intraoperative localization may be difficult, lesions other than rectal or cecal ones should probably be marked by preoperative tattooing. Further studies regarding the technique of tattooing are warranted.
One hundred and twenty-five strains of Vibrio parahaemolyticus carrying both the tdh and trh genes were selected from the strains isolated from the travelers with diarrhea by an hybridization test using polynucleotide probes. The levels of TDH produced by these strains and the association between the TDH levels and related characteristics in these strains were analyzed. The TDH level varied greatly from strain to strain, but none of the levels was as high as that of the typical Kanagawa phenomenon-positive strains. The strains were classified into "TDH producer" (18 strains), "Low-level TDH producer" (85 strains), and "No TDH producer" (22 strains) based on the results of a modified Elek test and the hemolysis assay on Wagatsuma agar. The highest TDH level achieved by the "TDH producer" was twofold lower than that of the Kanagawa phenomenon-positive strains as assayed by the RPLA method. All strains possessed the toxR gene. The trh1 and trh2 genes were detected in, respectively, 105 and 20 strains, and no correlation existed between the type of the trh gene and the levels of TDH produced. Considerable restriction fragment length polymorphism was observed with the tdh gene-bearing HindIII DNA fragment in different strains, but it was not related with the TDH level.
Some strains of Escherichia coli, Shigella spp., and Campylobacter spp. that have been implicated in diarrheal disease produce cytolethal distending toxin (CDT). CDT induces unique morphological changes in Chinese hamster ovary cells, but its association with diarrheal disease is unclear. We studied the diarrheagenicity of CDT using the cdt genes that we originally cloned from Shigella dysenteriae. The cdt genes were subcloned into a high-copy-number plasmid in E. coli JM109 to achieve high-level CDT production into the culture supernatant. An isogenic CDT- derivative was constructed by deletion of the 0.9-kb sequence internal to the cdt genes. A suckling mouse model was established, in which the intragastrically administered culture supernatant of the CDT+ E. coli strain induced excretion of loose and/or watery feces more often than did that of the CDT- strain in 24 h. The partially purified CDT preparation induced profuse watery diarrhea by 12 h in this model. High-level intestinal fluid accumulation in 4 h appeared to be related to the watery diarrhea. The results indicate that CDT is diarrheagenic to suckling mice and suggest that diarrheagenicity is dependent on CDT level. The preparations containing wild-type CDT induced tissue damage (necrosis and reparative hyperplasia) in the descending colon, whereas the tissues of the small intestines remained apparently intact. Association between the colonic damage and diarrhea is unclear and needs further investigation.
Active surveillance of Vibrio parahaemolyticus infection among hospitalized patients in Calcutta, India, was initiated in January 1994. The incidence of cases of V. parahaemolyticus infection suddenly increased in February 1996 and has remained high since then. One hundred thirty-four strains of V. parahaemolyticus isolated from January 1994 to August 1996 were examined for serovar, the presence of the thermostable direct hemolysin gene (tdh) and tdh-related hemolysin genes (trh1 and trh2), production of urease, and antibiogram. Strains of the O3:K6 serovar appeared for the first time in February 1996. The O3:K6 serovar strains accounted for 50 to 80% of the strains isolated during the high-incidence period (February to August 1996). All of the serovar O3:K6 strains carried the tdh gene but not the trh genes and did not produce urease. All of the isolates except two were sensitive to all of the antibiotics tested. These and the results of analysis by an arbitrarily primed PCR method indicated that the O3:K6 serovar strains belong to a unique clone. When the O3:K6 serovar strains, isolated from travelers arriving in Japan from Southeast Asian countries, were compared by the arbitrarily primed PCR method, the strains isolated between 1982 and 1993 were distinct from Calcutta O3:K6 while the strains isolated in 1995 and 1996 were indistinguishable from the Calcutta O3:K6 strains. The results suggest that this unique O3:K6 clone may have become prevalent not only in Calcutta but also in Southeast Asian countries very recently. Not only the O3:K6 strains but also the non-O3:K6, tdh-bearing strains isolated in 1996 produced thermostable direct hemolysin at high levels, and thus the level of hemolysin produced does not appear to have influenced the high incidence of serovar O3:K6 strains.
Urease-positive (Ure+) and urease-negative (Ure-) strains of Vibrio parahaemolyticus isolated from patients on the West Coast of the United States between 1979 and 1995 were analyzed for the thermostable direct hemolysin (tdh) gene and the tdh-related hemolysin (trh) genes (trh1 and trh2). The DNA colony hybridization method with the polynucleotide probes was used to determine the distribution of the genes. Of 60 Ure+ strains, 59 strains (98%) had the trh (either trh1 or trh2) gene and 54 strains (90%) carried the tdh gene. The absence of the trh gene or a related sequence in an exceptional Ure+ strain was confirmed by Southern blot analyses. The stronger correlation with the trh gene than with the tdh gene was mostly attributable to strains possessing only the trh2 gene. Of 25 Ure- strains, 20 strains (80%) had the tdh gene but none had the trh gene. These results indicate a very strong correlation between the Ure+ phenotype and the trh gene and are consistent with those reported for strains isolated in Asia. The Ure+ strains carrying the trh genes were not restricted to a unique group of the strains. The O4:K12 strains carrying the trh1 gene have predominantly been isolated since 1979. However, strains of various non-O4:K12 serovars carrying either the trh1 or the trh2 gene became predominant after 1992. In addition, analysis by the arbitrarily primed PCR method revealed two subgroups within the selected Ure+ O4:K12 strains. Hybridization tests with oligonucleotide probes demonstrated that the trh1 sequences of the West Coast strains differ to some extent from those of Asian strains. Nevertheless, a PCR method previously established to detect both the trh1 and the trh2 genes in Asian strains could detect 98% of those genes in the West Coast strains.
In 1993, Vanherweghem and his associates reported cases of rapidly progressive renal interstitial fibrosis in young women who were administered a slimming regimen including Chinese herbs. Subsequently, similar cases have been reported. In Japan, especially in the Kansai area, several cases of Chinese herbs nephropathy have already been reported. We experienced a patient suffering from Chinese herbs nephropathy (CHN), and further detected aristolochic acids from the Chinese herbs taken by the patient. Aristolochic acids are known to be causative agents of CHN. The danger of CHN should be noted as soon as possible and drugs containing aristolochic acids should be prohibited.
We compared the effectiveness of microwave tissue coagulation therapy (MTC) with the effectiveness of hepatectomy for patients with whole-liver multinodular hepatocellular carcinoma (HCC). The comparison was made using two sub-groups of 67 patients treated for multinodular HCC in the whole liver. One subgroup (group M, 17 patients) underwent MTC while another group (group H, 33 patients) underwent hepatectomy. The clinical stage of the liver in group M was significantly worse than in group H (p < 0.05), and the maximum diameter of HCC nodules in group M was significantly smaller than group H (p < 0.05). Survival rates of both groups were similar, but the group H disease-free survival rate was significantly better than that of group M (p < 0.05). Furthermore, the interval between treatment and tumor recurrence in group H was significantly longer than for group M (p < 0.05). We believe the more frequent incidence of local recurrence in group M may have been due to incomplete coagulation. Thus, MTC provides a possible new option for local treatment of HCC, but it is important to ensure complete coagulation of the tumors.