2.A Questionnaire Study of Medical Students' Comprehension of Clinical Genetics: The Necessity of Education in Clinical Genetics in Medical School
Atsushi WATANABE ; Takashi SHIMADA
Medical Education 2005;36(4):235-241
Because of the rapid progress in genetic research, only a small part of what is known about clinical genetics is taught in medical schools. At Nippon Medical School a clinical genetics course for fourth-year students started in October 2002. In the present study, we used a questionnaire to investigate how well second-year medical school students understand clinical genetics. The results of the questionnaire suggested that many students are confused about basic concepts in clinical genetics, such as the differences between inherited disease and diseased caused by genetic disorders and between hereditary and chromosomal disorders and also suggested that education in clinical genetics is needed in medical schools. In the United States, guidelines for teaching genetics in medical schools have been established. However, in Japan, considering the lack of consensus about medical genetics terminology, to disseminate correct knowledge about clinical genetics, the present situation of medical genetics education in medical schools must be clarified, and various other measures, such as establishing what information should be taught, should be carried out.
3.Food and Drug Interactions: Effect of Acanthopanax senticosus Harms on CYP2C9 Activity (Part 2)
Tsunehisa TAKAHASHI ; Takashi SATOH ; Kazuhiro WATANABE
Japanese Journal of Complementary and Alternative Medicine 2014;11(1):9-15
Objective: Acanthopanax senticosus Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity.
Methods and Results: CYP2C9-catalyzed diclofenac 4′-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4′-hydroxylase in HLM revealed that ASE addition significantly decreased Vmax but had no effect on Km. These results suggest that diclofenac 4′-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4′-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4′-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration.
Conclusion: These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.
4.Study of factors related to renal dysfunction following operation for thoracic aortic aneurysm.
Hiroshi URAYAMA ; Yoh WATANABE ; Takashi IWA
Japanese Journal of Cardiovascular Surgery 1988;18(3):319-324
During past 15 years 78 patients were operated for thoracic aortic aneurysm. Patients operated in emergency or dead within 24 hours after operation or with preoperative renal failure were excluded and remaining 65 patients were studied for factors affecting postoperative renal dysfunction. Postoperative renal dysfunction was based on the serum creatinine value which was within normal limit before operation and exceeded 1.5mg/dl after operation, or which increased by 1mg/dl and more from preoperative value. 23 patiens developed postoperative renal dysfunction and the incidence was 35.4%. As preoperative factors, old age, male and high value of preoperative serum creatinine were significantly (p<0.01) related with postoperative renal dysfunction. As intraoperative factor, decreased urine output per operative hour was significantly (0.01<p<0.05) related. Other preoperative factors; hypertension, diabetes, location of aneurysm, dissecting and nondissecting, intraoperative factors; operation time, volume of operative bleeding, minimum systolic blood pressure during operation, clamping time of aorta, minimum temperature of rectum, difference of adjuncts (temporary shunt or extracorporeal circulation), postoperative factors; systolic blood pressure at arriving ICU, urine output of first postoperative day were not significantly related. Between the operative procedures of graft replacement and extraanatomic bypass, no significant difference was recognized in occurrence of postoperative renal dysfunction, but patients with patch angioplasty etc. developed no renal dysfunction. In the complications within one week after operation, central nervous system dysfunction, infection and hemorrhage had a tendency to occur together with renal dysfunction. For prevention of postoperative renal dysfunction it is important to minimize the renal ischemia, to protect the kidney and to maintain urine output during operation, particularly in patients of preoperative decreased function of kidney and of old male with advanced arteriosclerosis. Also it is necessary to choose the less invasive procedure of operation for patients of severely decreased function of kidney and to consider about organ system relations in patients of postoperative renal dysfunction.
5.A Case Report of Abdominal Aortic Aneurysm with Isolated Left-side Inferior Vena Cava.
Takashi Hattori ; Yasunori Watanabe ; Shinya Kanemoto
Japanese Journal of Cardiovascular Surgery 1997;26(3):204-206
Isolated left-side inferior vena cava is rare, there being only four cases associated with abdominal aortic aneurysm reported so far in the Japanese literature. A 72-year-old man was admitted to our hospital for the evaluation of an abdominal pulsatile mass. CT scan revealed abdominal aortic aneurysm with isolated left-sided inferior vena cava. Aneurysmectomy and bifurcated graft replacement was performed with retracting inferior vena cava. The postoperative course was uneventful.
7.Effects of electronic moxibustion on immune response (II)
Shinichiro WATANABE ; Takashi MATSUO ; Hiroshi HARA ; Katsumi HIROSE ; Shimetaro HARA
Journal of the Japan Society of Acupuncture and Moxibustion 1982;32(1):20-26
In the previous papers, we reported the effects of electronic moxibustion on immune response of experimental rats to the exogeneous antigens, human γ-globulin.
The results supported the theory, “non-specific heat aggregeted autologous tissue protein stimulation therapy” presented by Dr. Shimetaro Hara in 1933.
Therefore, in this paper we chose two kinds of antigens, one is the T-cell dependent antigen, dinitrophenylated keyhole limpet hemocyanin (DNP-KLH), the other is the T-cell independent antigen dinitrophenylated Ficoll (DNP-Ficoll) to analyse the mechanism of electronic moxibustion whether it enhances the immune response or not.
Using 9 weeks old femal SLC-Wistar rats, we administered the electronic moxibustion according to the method reported in the previous papers. Following daily moxibustion for 8 weeks, antigens were giver twice at intervals of one week together with Freund's complete adjuvant. And 4 days later from the last antigen stimulation direct, DNP plaque forming cells in the spleen were counted.
The results obviously showed daily electronic moxibustion for 8 weeks enhanced immune response against the T-cell dependent antigen (DNP-KLH) stimulated rats but no effect on the immune response to the T-cell independent antigen (DNP-Ficoll) stimulated rats.
The daily electronic moxibustion for 4 weeks to rats failed to show any effective results against both antigens stimulation.
The responses of spleen cells against mitogenic lectins, PHA, Con A and PWM were analysed 3 days after the incubation with lectins by tritiated thymidine up takes into cells. The results also showed the animal group received the electronic moxibustion for 8 weeks manifested higher response against the one of T-cell mitogens, Con A compared with either the group received the electronic moxibustion for 4 weeks or the control group, not received any treatment.
These results suggested that the immune activation mechanism exhibited by the electronic moxibustion is via the activation of T-cell function and the electronic moxibustion does not act on B cell nor antibody forming cells.
The direct effects on the animal skin by the electronic moxibustion were shown exactly the same physical characteristics as the conventional moxibustion method as reported in the previous papers. Therefore, we could expect the similar T-cell activation effect on the immune response by the conventional moxibustion.
But from our results to get such a T-cell activation by the electronic moxibustion, it has been necessary to administrate the electronic moxibustion daily at least for more than 4 weeks.
Next we would like to make clear what kinds of subpopulation in the T-cell populations are activated by the electronic moxibustion.
Before the clinical administration of the electronic moxibustion as one of immune activators, it is necessary to investigate further about the optimal amounts of the moxibustion, effects of the moxibustion on the cellular immunity or tumor immunity.
8.Food and Drug Interactions: Effect of Acanthopanax senticosus Harms on CYP3A4 and CYP2C9 Activities (Part 3)
Tsunehisa TAKAHASHI ; Masaki IGARASHI ; Takashi SATOH ; Kazuhiro WATANABE
Japanese Journal of Complementary and Alternative Medicine 2014;11(1):17-24
Objective: By using human liver microsomes (HLM), we analyzed the effects of 14 known components of A.senticosus Harms on the activities of CYP2C9 and CYP3A4.
Methods and Results: Sesamin and quercetin inhibited both enzyme activities, whereas quercitrin strongly inhibited CYP3A4 activity. The 50% inhibitory concentrations (IC50s) of sesamin and quercetin on CYP2C9 activity were approximately 124- and 59-fold higher and the IC50s of sesamin, quercetin, and quercitrin on CYP3A4 activity were approximately 427-, 135-, and 22-fold higher than that of A. senticosus Harms extract (ASE), respectively. All these components inhibited both CYP3A4 and CYP2C9 in a non-competitive manner. However, these components are present in small amounts in ASE.
Conclusion: Therefore, the food-drug interactions caused by A. senticosus Harms are presumed to be due to the additive or synergistic interaction of these components or the other existing components, including their metabolites.
9.Black Tea Inhibits Small Intestinal α-Glucosidase Activity in db/db Mouse
Masaki IGARASHI ; Takashi SATOH ; Hiroshi YAMASHITA ; Kazuhiro WATANABE
Japanese Journal of Complementary and Alternative Medicine 2014;11(1):25-33
The inhibitory effects of the freeze-dried powder of the aqueous extract of black tea leaf (JAT) on α-glucosidase activity were investigated. We initially examined the effects of JAT addition on yeast α-glucosidase activity. JAT significantly and dose-dependently inhibited α-glucosidase activity and more strongly inhibited the activity than acarbose, the positive control. Then, we examined the effects of oral administration of JAT on sucrose tolerance in type 2 diabetes mellitus model db/db mice. Both JAT and acarbose administered groups showed a dose-dependent decrease in plasma glucose levels after the sucrose loading compared with the control group. Notable was that the plasma glucose levels of the 500 mg/kg JAT administered group exhibited a significant decrease 30 min or longer after the sucrose loading. On the other hand, no significant difference in plasma insulin levels was seen between the JAT administered group and the control group. We also measured small intestinal sucrase activity in db/db mouse at 30 min after JAT oral administration. Compared to control mice, small intestinal sucrase activity was significantly decreased in the 500 mg/kg JAT administered mice. These findings indicate that JAT may be a useful natural material for the prevention and therapy of type 2 diabetes mellitus.
10.Initial Results of Thoracic Endovascular Repair with the Gore TAG Device Evaluated by the Japan SCORE System
Hirofumi Midorikawa ; Megumu Kanno ; Takashi Takano ; Kouyu Watanabe ; Yuzo Shimazu
Japanese Journal of Cardiovascular Surgery 2010;39(4):172-176
We report the initial results of thoracic endovascular repair using the Gore TAG device (TAG) used in treatment of thoracic aortic aneurysms (TAA), and evaluate initial outcome based on the Japan SCORE (JS) system. From August 2008 to July 2009, thoracic aortic endovascular repair (TEVAR) for TAA was applied in 27 cases (men/women, 22/5, 53-88 years old, mean age 70.5). Locations included the distal arch in 7 cases, proximal descending TAA (dTAA) in 12 cases and middle or distal dTAA in 8 cases. Deployment of a stent-graft (SG) was successful in 27 cases (100%) and complete thrombosis of the aneurysm or complete entry closure was achieved in 26 cases (96.3%). There was 1 type 2 endoleak (3.7%), 2 iliac arterial injuries (7.4%) and 2 cases of temporary hemodialysis (7.4%). There was no occurrence of paraplegia or hospital death. The 30-day mortality rate and major complication rate examined by the Japan SCORE (JS) system did not show any statistical differences between the TEVAR group and the open repair (OR) group, however the data were higher in the TEVAR group, although not statisfically in the OR group. The OR group had a high complication incidence in comparison with the TEVAR group. Based on evaluation by the JS system, the initial results suggest that TAG for the treatment of TAA is superior to conventional open surgery.