[A case of occult insulinoma localized by intra-arterial stimulation with calcium and venous sampling technic].
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Biomedical subjects
Publications and source records attributed to A Uchida.
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We have experienced 7 cases of laparoscopic adrenalectomy for adrenal tumors during the past two years since our department opened in July, 1992. In four cases, the tumors were clinically diagnosed preoperatively as primary aldosteronism and in the other three cases as endocrine-inactive tumors. Four tumors were found on the left adrenal and three on the right. Five tumors were successfully resected with laparoscopic surgery, but in the other two cases it was immediately followed by open surgery because of an uncontrollable hemorrhage. Laparoscopically unresected tumors existed, one on the right and the other on the left adrenal. The average operation time for laparoscopic adrenalectomy was twice as much as that of open adrenalectomy previously performed. However, the operation time has been recently shortened to be less than 200 minutes. Hemorrhage during the operation was rather less in laparoscopic surgeries if they were successfully done. Postoperative recovery was found to be much faster and the hospital stay was shortened by more than 10 days in patients operated with a laparoscope. These findings indicate that laparoscopic adrenalectomy is a minimally invasive operation that can increase the QOL's of the patient. Although we consider that this operation may propagate as a method for adrenalectomy in future, it must be performed with a careful backup system in the case of an emergency.
A 62-year-old male patient presented with a complaint of the lower abdominal distention. Ultrasonography demonstrated bilateral hydronephroses and a huge heterogeneous mass in the pelvic cavity. Excretory urogram showed left-non visualized kidney and right-hydronephrosis. CT showed a heterogenous mass, situating 25 cm in diameter, adjacent to the left side of the bladder. Tumor resection was carried out on May 17th of 1994. Histopathological diagnosis of the surgical specimen was abdominal desmoid with HE stain.
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Quercetin, a widely distributed bioflavonoid, inhibits the growth of tumor cells. The present study was designed to investigate the possible involvement of apoptosis and heat shock protein in the antitumor activity of quercetin. Treatment with quercetin of K562, Molt-4, Raji, and MCAS tumor cell lines resulted in morphological changes, including propidium iodide-stained condensed nuclei (intact or fragmented), condensation of nuclear chromatin, and nuclear fragmentation. Agarose gel electrophoresis of quercetin-treated tumor cells demonstrated a typical ladder-like pattern of DNA fragments. In addition, the hypodiploid DNA peak of propidium iodide-stained nuclei was revealed by flow cytometry. Quercetin induced apoptosis in cells at G1 and S in a dose- and time-dependent manner. The apoptosis-inducing activity of quercetin was enhanced by cycloheximide and actinomycin D. A nuclease inhibitor, aurintricarboxylic acid, inhibited quercetin-induced apoptosis, whereas deprivation of intracellular calcium by EGTA had no effect. 12-O-Tetradecanoylphorbol-13-acetate and H-7 did not affect the induction of apoptosis by quercetin. The synthesis of HSP70 was inhibited by quercetin when determined by immunocytochemistry, Western blot analysis, and Northern blot analysis. Quercetin-treated tumor cells were not induced to show aggregation of HSP70 in the nuclei and nucleolus in response to heat shock, resulting in apoptosis. By contrast, when tumor cells were first exposed to heat shock, no apoptosis was induced by quercetin. In addition, pretreatment of tumor cells with HSP70 antisense oligomer that specifically inhibited the synthesis of HSP70 enhanced the subsequent induction of apoptosis by quercetin. These results suggest that quercetin displays antitumor activity by triggering apoptosis and that HSP70 may affect quercetin-induced apoptosis.
In order to define the significant factors for a staging system of soft-tissue sarcomas (STS), histologic and clinical findings in 190 adult patients with localized STS in the extremities and trunk were reviewed. The male-to-female ratio was 1.21. The histologic grading of tumors was defined according to the criteria recently proposed by us: tumors were low-grade in 65 cases, intermediate-grade in 57 cases and high-grade in 68 cases. The initial surgical procedure was as follows: intracapsular excision in 9 cases, marginal excision in 104 and wide local excision in 77, including 15 amputations. The mode of treatment was surgery alone (101 patients), surgery and chemotherapy (58), surgery and radiotherapy (22) and surgery and combined chemo- and radiotherapy (9). Univariate analysis revealed histologic grade, sex, tumor size and tumor depth to be significant prognostic factors. Multivariate analysis revealed histologic grade to be the only independent factor for prognosis. Significant clinical factors in each histologic grade were then evaluated. In the low-grade group, local recurrence significantly affected prognosis. Most of the patients with local recurrence had had marginal resection as the initial surgical procedure. No clinical factors affecting prognosis in the intermediate-grade group could be determined. In the high-grade group, patients with wide local excision and adjuvant chemotherapy had a better prognosis than those with marginal excision with or without adjuvant chemotherapy and wide local excision without chemotherapy (p = 0.09). In conclusion, histologic grade was the only significant factor for the staging of STS. On the basis of our staging system, different modalities of treatment for each grade of STS might be indicated; adequate surgery is essential for the prevention of local recurrence, which resulted in reduced mortality in patients with low-grade STS. For high-grade STS, the prevention of distant metastasis by combined extensive surgery and adjuvant chemotherapy may make long-term survival possible.
We have developed reasonably strong but bioabsorbable osteosynthetic screws, pins and nails made of ultra high strength poly-L-lactide (PLLA) and evaluated their use in 143 patients. The PLLA implants have the highest strength among those reported to date. They lose about 10% of their initial strength within 8 weeks, about 40% within 4 weeks and nearly 100% within 20 weeks in vivo. The patients were aged from 9 to 78 years, and the follow up was from 2 to 6 years. The implants were used for fixation of bone grafts in 84 patients, peri- and intra-articular fractures in 49, after osteotomy in 8, and in 2 others. Bony union was not achieved in only one case. In the early stages of the study, breakage of screws occurred in 12 cases (8%), mostly because of an inappropriate size of tap; these problems have not occurred after improvement of the tapping system. There were no cases with abnormal blood tests, infection or foreign body reaction.
The "a" subunit of human coagulation factor XIII (F13A) exhibits genetic polymorphism defined by four common alleles, F13A*1A, *1B, *2A, and *2B. We have previously suggested on the basis of the isoelectric focusing patterns of the four allele products that point mutations at two separate sites and one intragenic crossing over might be involved in the genes of F13A polymorphism. Here, we report nucleotide substitutions associated with F13A polymorphism. A C/T transition of the second nucleotide of codon 564 in exon 12 is responsible for the difference between F13A*1A and *1B and that between F13A*2A and *2B, and a set of two base changes in codons 650 and 651 in exon 14 leads to the differences between F13A*1A and *2A and those between F13A*1B and *2B. The four combinations of the point mutations at the two exons thus correspond to the four alleles, two of which were generated by the point mutations from ancestral monomorphic gene. The results suggest strongly that intragenic crossing over must be involved in the genesis of the fourth allele. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods discriminating these base changes in exons 12 and 14 are also presented.
The activity of blood lymphocytes to kill autologous freshly isolated tumor cells tested at the time of surgery predicts a favorable clinical course in patients who have primary localized solid tumor and receive curative operation. The strong correlation of autologous tumor killing (ATK) activity with disease-free interval and total survival indicates that ATK activity is a meaningful prognostic indicator and provides evidence for immunological control of tumor growth and metastasis. Although there is no direct evidence that ATK lymphocytes play a critical role in regression of tumor and prevention of tumor regrowth, the lack of ATK activity in patients who relapsed and died may not result from other factors related to their poor performance status, immune functions and tumor characteristics. Clinical trials with ATK induction therapy resulted in an improvement of the clinical outcome in patients who naturally have no such potential. The data indicate that the presence of both natural and induced ATK activity is strongly associated with long-term survival. In addition, adoptive transfer of BRM-induced ATK effector cells resulted in prolongation of survival time even in patients with documented metastatic tumors. Thus, considerable emphasis should be placed on a strategy that induces ATK activity in vivo. Such an approach may provide a new focus for cancer immunotherapy.
OBJECTIVE: To study the relationship between some ovarian morphological findings based on transvaginal ultrasound (US) and the clomiphene citrate (CC) responsiveness in patients with polycystic ovarian syndrome (PCOS). DESIGN: A comparative study of ovarian US features between the CC responders and the CC nonresponders. SETTING: Infertility and Endocrine Clinic, Department of Obstetrics Gynecology, Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Forty-seven infertile patients with PCOS and 30 healthy volunteers. INTERVENTIONS: A dose of 50 to 200 mg/d CC was given for ovulation induction in patients with PCOS. MAIN OUTCOME MEASURES: Ovarian volume and number of follicles; serum LH, FSH, T, delta 4 androstenedione, and DHEAS. RESULTS: The mean ovarian volume (11.9 mL) and the number of small follicles (13.0) were significantly larger in the CC nonresponders compared with those of the CC responders (7.9 mL and 7.0, respectively). Only 47% of the CC responders and 79% of the CC nonresponders had bilaterally enlarged ovaries (> 6.2 mL). Considerable overlap existed between the different groups. However, 96% of the CC nonresponders had a significantly increased number of follicles (> or = 10 follicles) in each ovary compared with that (16%) of the CC responders. Furthermore, with the combination of these parameters, none of the CC nonresponders had bilaterally normal ovaries, and 96% of patients with PCOS with bilaterally abnormal ovaries were CC nonresponsive. CONCLUSIONS: Small multiple follicles (> or = 10) and enlarged ovarian volume (> 6.2 mL) were the most prominent transvaginal US features of ovaries in patients with PCOS with CC nonresponsiveness. These US features could be clinically useful for distinguishing clearly a CC nonresponder from a CC responder.
Tetraplegic wheelchair basketball was started in the Kanagawa Rehabilitation Center (KRC) as a recreational sport for tetraplegics in 1980. In this game, there are two goals on each side, thus we call it 'twin basketball'. One goal is of ordinary height and the other is low. Three ways of shooting and two ways of dribbling are allowed according to the player's level of tetraplegia and technical skill. The first official game was held in 1983. Since then, the game has been taken up in several areas of Japan. The first All Japan championship game was held in 1987, ten teams including 98 tetraplegics attending. Five years later, in the sixth championship game, 18 teams including 171 tetraplegics attended. As official physicians, we have examined the physical condition and technical skills of all players since 1987. All players are classified, and assigned points from 1 to 4.5. The total number of points of five players in one team are limited to 11.
The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high-cholesterol diet developed marked hypercholesterolemia and hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats.
We investigated retrospectively the relationship between the ultrasonographic appearance of the ovaries and histopathological findings in patients with polycystic ovarian syndrome (PCOS) and compared these histopathological findings with endocrine concentrations. A total of 20 patients with PCOS were studied. Each patient had a history of infertility, menstrual disturbance and > 10 small cysts in each ovary that were detected by transvaginal ultrasound. Ovarian ultrasound appearance was classified as a general cystic pattern (GCP) or peripheral cystic pattern (PCP). Histological examination of specimens from patients undergoing ovarian wedge resection by laparotomy were compared with ultrasonographic images. In 15 of the 16 ovaries with GCP, the histopathological findings were consistent with the ultrasonographic images. In all 24 ovaries with PCP, the histopathological and ultrasonographic images were consistent. The mean ovarian capsular thickness was significantly higher in the GCP than the PCP. Androstenedione was significantly higher in the GCP than the PCP, whereas the ratio of luteinizing hormone to follicle-stimulating hormone was significantly higher in the PCP than the GCP. Therefore, our results suggested that GCP and PCP correspond to histopathological differences. Histological GCP and PCP appear to differ endocrinologically.
To clarify the influence of small follicular cysts in ovaries on endocrine in ovulatory patients with multifollicular ovaries (MFO), the comparative study of endocrine among ovulatory patients with MFO and anovulatory patients with polycystic ovarian syndrome (PCOS) were examined. In ovulatory patients with MFO, there was no significant correlation between the increase in the number of ovarian cysts and gonadotropin levels, however, estrone and androgen levels tended to increase as the number of cysts increased. LH levels in PCOS were significantly higher than those in patients with more than 10 small cysts; however, there was no significant difference in androgen levels between the two. It was suggested that MFO is a progressive disease and that the presence of more than 10 small follicular cysts in each ovary in ovulatory women may be latent PCOS.
Controversy still exists concerning the therapy for viral myocarditis which manifests a wide variety of clinical symptoms. Vesnarinone, a quinolinone derivative that was developed as a positive inotropic agent with complex actions, including phosphodiesterase inhibition and cation channel modification, has recently been confirmed to improve the prognosis of patients with chronic heart failure. However, the precise mechanism of this beneficial effect is not yet clearly understood. In this study, using a murine model of acute viral myocarditis resulting from encephalomyocarditis virus infection, survival and myocardial damage were markedly improved by treatment with vesnarinone. In contrast, survival was not improved by treatment with amrinone, a phosphodiesterase inhibitor. Although vesnarinone did not inhibit viral replication or protect myocytes from viral direct cell injury, it did inhibit the increase in natural killer cell activity after viral infection. On the other hand, amrinone failed to inhibit natural killer cell activity. Both vesnarinone and amrinone suppressed the production of tumor necrosis factor-alpha. Therefore, we postulate that vesnarinone exerted its beneficial effects through an inhibition of natural killer cell activity, and that it serves as an immunomodulator providing new therapeutic possibilities for the treatment of viral myocarditis and/or immunological disorders.
Inhibitory action of leminoprazole ((+/-)-2-[[2-(isobutylmethylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, LEM) against the H+,K(+)-ATPase activity in rabbit gastric vesicles was investigated. LEM inhibited the H+,K(+)-ATPase activity in leaky vesicles in a concentration- and time-dependent manner. When preincubated with gastric vesicles (20 micrograms protein/ml) for 30 min at 37 degrees C in medium (pH 6.1 or 7.4), the IC50 values were 5.3 microM and 19 microM, respectively. The inhibitory action of LEM was not competitive with respect to K+ and was not reversed by dilution, suggesting that the inhibitory action is irreversible. Inhibition of the enzyme activity by LEM was not found when beta-mercaptoethanol (0.1 mM) was premixed with enzyme before addition of LEM, and it was partially recovered by addition of beta-mercaptoethanol or dithiothreitol (50 mM) after LEM treatment. These results suggest that LEM reacts with essential SH groups of H+,K(+)-ATPase and inactivates the enzyme by forming a covalent disulfide bond. The inhibitory activity of LEM was more potent at pH 6.1 than at pH 7.4, and the rate of the reaction of LEM with GSH was enhanced by lowering the pH of the medium. The inhibition of proton transport by LEM (30 microM) was found after the intact vesicles were fully acidified. LEM also strongly inhibited the valinomycin-stimulated H+,K(+)-ATPase activity. Therefore, it is considered that LEM inhibits H+,K(+)-ATPase activity by an unknown activated reaction under the acidic condition. Alternatively, the possibility was also suggested that an acidic condition is not always necessary for the inhibition of H+,K(+)-ATPase activity by LEM, since LEM, at higher concentration, inhibited the initial rate of acidification and inhibited nigericin-stimulated H+,K(+)-ATPase activity in intact vesicles.
The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+,K(+)-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+,K(+)-ATPase activity, and their IC50 values were 31 microM and 24 microM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+,K(+)-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+,K(+)-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+,K(+)-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+,K(+)-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+,K(+)-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+,K(+)-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+,K(+)-ATPase activity to the same degree as the single administration.
We investigated the effect of NC-1300-O-3 on gastric mucus secretion and prostaglandin release into the gastric lumen in rats. NC-1300-O-3 following single or repeated administration for up to 4 weeks significantly increased the hexose content in the gastric lumen at 10 to 100 mg/kg, p.o. Omeprazole and cimetidine at doses that strongly inhibited gastric acid secretion had no effect on the hexose content following single or repeated administration for 8 days. When administered repeatedly for 8 days, NC-1300-O-3, omeprazole and cimetidine significantly decreased the hexosamine content in gastric surface mucosa, but significantly increased gastric mucus secretion was observed at the same time only with NC-1300-O-3, indicating that this agent has a profile of action on gastric mucus metabolism different from those of omeprazole and cimetidine. NC-1300-O-3 at 10 and 30 mg/kg, p.o. and omeprazole at 30 mg/kg, p.o. increased the release of prostaglandins into the gastric lumen, and this was markedly inhibited by pretreatment with indomethacin, suggesting that these agents may enhance prostaglandin biosynthesis in the gastric mucosa. From these results, it seems that the enhancement of NC-1300-O-3 on gastric mucus secretion and prostaglandin biosynthesis in the gastric mucosa contribute to the antiulcer effect of NC-1300-O-3.