Biomedical subjects
Publications and source records attributed to K Shindo.
A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo.
We report a rare case of microcystic meningioma presenting with atypical neuroradiological features. A 76-year-old woman was admitted to our hospital in October, 1996 because of head heaviness without obvious neurological deficits. Previous CT scan in 1989 revealed no abnormality, but a subsequent scan in 1992 showed a low-density area in the right frontal region. Since then the patient has been followed up as a case of cerebral infarction. At the time of the current admission, CT scan disclosed the low-density area as having grown to the size of 4 cm and heterogeneously enhanced after injection of contrast medium. On MRI the mass lesion was depicted as low-intensity on T1-weighted image and high-intensity on T2-weighted image. The mass was heterogeneously enhanced after administration of Gd-DTPA. Right internal and external carotid angiograms revealed neither tumor feeder nor tumor stain. Craniogram showed neither hyperostosis nor bone erosion, and yet bone scintigram demonstrated markedly increased uptake involving the right frontal bone near the tumor. At surgery the tumor was found to have originated from the dura in the right frontal convexity, which was well demarcated and separated from the surrounding brain tissue. Total removal designated as Simpson grade I procedure was accomplished. Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas. The microcysts were seen to reside in the extracellular spaces rather than in the cytoplasm. With these pathological findings, the tumor was finally diagnosed as microcystic meningioma.
Renal transplantation was performed in a 24-yr-old woman with type AA systemic amyloidosis. Renal biopsy at 11 yr post-transplantation showed no amyloid recurrence, but the presence of mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Renal function was satisfactory with the exception of mild proteinuria. Symptoms related to systemic amyloidosis including goiter and cardiac deposition, improved post-transplantation. Renal transplantation is the recommended therapy for type AA systemic amyloidosis.
A venous cuff technique was applied only for venous drainage in orthotopic small bowel transplantation of rats. Rates of technical failure (death within 4 days) and in clinical signs were compared between the groups with (group A) and without (group B) venous cuff technique. Technical failures with and without venous cuff technique were 5% and 25%, respectively. Mean survival days, excluding deaths from technical failure, were 9.2 +/- 2.3 in group A and 8.1 +/- 2.6 days in group B. No significant differences were observed in mean survival days or in weight loss between the two groups. Acute rejection was the cause of death in both groups. Since the model with venous cuff technique showed low mortality, it could be widely employed in small bowel transplantation studies.
Explore the source record for details and available documents.
This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.
PURPOSE: Functional outcome after anterior resection for rectal cancer is improved by colonic J-pouch reconstruction compared with straight anastomosis. The indications for colonic J-pouch reconstruction have yet to be determined. Therefore, we attempted to determine the level at which J-pouch reconstruction provides an advantage over straight anastomosis. METHODS: A total of 48 patients who underwent 5-cm colonic J-pouch reconstruction (J-pouch group) and 80 patients who underwent straight anastomosis (straight group) underwent functional assessment one year postoperatively. RESULTS: The functional outcome in the J-pouch group was significantly better than that in the straight group when the distance of the anastomosis from the anal verge was less than 8 cm. The difference was particularly obvious when the level of the anastomosis was below 4 cm. However, functional outcome in the straight group when the anastomosis was between 9 and 12 cm from the anal verge was also satisfactory and did not differ from that in the J-pouch group when the anastomosis was between 5 and 8 cm from the anal verge. CONCLUSIONS: Colonic J-pouch reconstruction is indicated when the distance of anastomosis from the anal verge is less than 8 cm, and it is essential when the distance is less than 4 cm.
PURPOSE: In surgery for rectal cancer, it is unclear whether the inferior mesenteric artery should be ligated at a high or low position. The study contained herein was undertaken to clarify the indications for high ligation of the inferior mesenteric artery. METHODS: Subjects included 198 patients with rectal cancer who underwent resection with high ligation of the inferior mesenteric artery. Nodal metastases were examined by the clearing methods. RESULTS: The incidence of metastases to the lymph nodes surrounding the origin of the inferior mesenteric artery (root nodes) was 8.6 percent. Inferior mesenteric artery root nodal metastases occurred more frequently with pT3 and pT4 cancer. The five-year survival rate in patients with inferior mesenteric artery root nodal metastases was 38.5 percent; this rate was significantly lower than in those without inferior mesenteric artery root nodal metastases (73.4 percent). CONCLUSIONS: Although the five-year survival rate in patients with inferior mesenteric artery root nodal metastases was lower than in those without metastases, inferior mesenteric artery root nodal dissection should be performed after high ligation of the inferior mesenteric artery for patients with pT3 and pT4 cancers.
In anterior resection with anastomosis using the double-staple technique for low-lying rectal cancer in male patients, the approach to the anal canal with a stapling instrument via the abdominal area is limited by the narrow pelvis. The stapling and transection of the anal canal via the posterior transsacral approach prior to performing an anterior resection thus enables the lower rectum and anal canal to be visualized, so that the anal canal can be accurately stapled and transected even in male patients with a narrow pelvis.
We conducted overnight polysomnographic sleep studies of 16 patients (5 men and 11 women) with clinically well-controlled myasthenia gravis (MG). The subtypes of MG were IIA (3 patients), IIB (11 patients), IV (1 patient) and V (1 patient). Twelve patients were found on polysomnography to have obstructive and/or central types of the sleep apnoeas (SA). Their mean age was 42.4, SD 16.4 years, and the mean duration of MG was 7.4, SD 6.96 years. SA was not detected in 4 patients whose mean age was 30.8, SD 10.71 years and who had manifested MG for a mean duration of only 0.9, SD 0.65 years. Thus, patients with a longer duration of MG tended to have more SA. In 9 of the 12 SA patients, polysomnographic studies were repeated following thymectomy. SA had resolved in 6 patients, but persisted in 3. These findings suggest that SA is a possible clinical manifestiation of MG and that nocturnal dysfunction of both peripheral and central colinergic systems may be involved.
Explore the source record for details and available documents.
Effect of oxatomide on release and production of platelet-activating factor (PAF) in neutrophils obtained from asthmatic and non-asthmatic patients was investigated. Neutrophils were preincubated with or without oxatomide and stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (f-MLP, 10 microM) for 15 min. PAF activity was detected by aggregation of washed guinea pig platelets. PAF activity released from asthmatic neutrophils without preincubation of oxatomide was 7.97[0.22] (mean[SEM], ng/10(7) cells) in supernatants and 33.4[0.26] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of oxatomide, PAF activity reduced to 6.77[0.37] (mean[SEM], ng/10(7) cells), 3.99[0.25], and 0.96[0.05] (n = 15) in the supernatants, and 22.4[0.31], 16.7[0.22], and 6.35[0.11] (n = 15) in the cell pellets, respectively. PAF activity in non-asthmatic neutrophils without preincubation of oxatomide was 6.35[0.12] (mean[SEM], ng/10(7) cells) in supernatants and 27.9[0.25] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of oxatomide, PAF activity reduced to 5.02[0.16] (mean [SEM], ng/10(7) cells), 3.96[0.11], and 0.94[0.03] (n = 10) in the supernatants, and 28.4[0.69], 13.78[0.17], and 2.88[0.27] (n = 10) in the cell pellets, respectively. Our results showed that preincubation with oxatomide caused a dose-dependent inhibition of intra- and extracellular PAF activity from asthmatic and non-asthmatic neutrophils in the same manner.
Our objective was to determine the effect of amphotericin B on leukotriene (LT) A4 hydrolase in human neutrophil cytosol and to examine its effect on intact neutrophils in vitro. Cytosolic fractions were assayed for LTA4 hydrolase and 5-lipoxygenase activity in the presence or absence of amphotericin B. The IC50 of amphotericin B for LTA4 hydrolase activity was 0.72 microM. No inhibition of 5-lipoxygenase activity in the cytosolic fraction was detected. The IC50 of amphotericin B for leukotriene B4 synthesis in intact neutrophils was 0.43 microM. The 5-hydro(per) oxy-eicosatetraenoic acid (5-H(P)ETE) synthesis was diminished in intact cells by 66.8 [3.4]% (mean[SEM]) in the presence of 0.01 mM amphotericin B. Thus, amphotericin B inhibited the synthesis of LTB4 and 5-H(P)ETE in neutrophils in vitro. Differences between the results of studies on cytosol and on intact cells suggest that amphotericin B is involved in a complex interaction in the intact cell.
To estimate the effect of prednisolone on 5-lipoxygenase activity in eosinophils obtained from asthmatic patients, cytosolic levels of 5-H(P)ETE and Ca2+ were measured in the eosinophils which were exposed to prednisolone in vitro and in vivo. The mean level of 5-H(P)ETE during a wheezing attack was significantly lower in the patients who had received intravenous prednisolone (500 mg/day). Incubation with prednisolone in vitro caused a dose-dependent decrease in the cytosolic levels of 5-H(P)ETE and Ca2+ in eosinophils obtained during the wheezing attack, but not in the eosinophils obtained from during remission. Results suggest that prednisolone inhibits the level of 5-H(P)ETE in the eosinophil cytosols of asthmatic patients during a wheezing attack, probably by inhibition of 5-lipoxygenase activity which is involved in the reduction of the influx of Ca2+.
PURPOSE: To clarify the clinical usefulness of the dipole tracing method in evaluation of interictal EEG spikes in patients with partial epilepsy. METHODS: Eight patients with partial epilepsy were studied. We compared the generator source of interictal spikes detected by the dipole tracing method with the results of magnetic resonance imaging (MRI), interictal/ictal measurement of cerebral blood flow (CBF) by single photon emission computed tomography (SPECT), interictal measurement of glucose metabolism by positron emission tomography (PET) and invasive electrocorticogram (ECoG). RESULTS: In 5 patients with mesial temporal lobe epilepsy (TLE), including 3 patients who underwent standard temporal lobectomy, the dipole tracing method showed results consistent with those of other examinations and better correlation with ECoG than with other noninvasive examinations. In a patient with mesial TLE who had defects in the skull due to previous surgery, the dipoles were located more laterally than expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to have an epileptogenic area in the lateral frontal area, the spike dipoles were identified in the medial side of the frontal lobe. CONCLUSIONS: The dipole tracing method used in the present study is useful for localizing epileptogenic areas in patients with mesial TLE. However, in patients with partial skull defects and in those with FLE, the reliability of this method is still in accuracy of the lobe level.
BACKGROUND: It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora. AIMS: To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism. METHODS: Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover on the tip and deconjugation was examined using thin layer chromatography. Fat malabsorption was detected by a triolein breath test. RESULTS: In the bile acid breath test, expired breath samples from all patients and healthy volunteers showed significantly greater 14CO2 specific activity after omeprazole treatment (20 mg/day) than before treatment. Bacterial overgrowth was found in the jejunal fluid and gastric juice of both ulcer patients and healthy volunteers after omeprazole treatment. The following species were identified: Escherichia coli, Candida albicans, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, Eu parvum, and Corynebacterium granulosum. All of these species, except E coli and C albicans, deconjugate bile acids. There was a significant correlation between 14CO2 activity and gastric pH, both before and after omeprazole treatment in both groups. The triolein breath test revealed impaired fat absorption in both groups after omeprazole treatment. CONCLUSIONS: Both patients with gastric ulcer and healthy volunteers exhibited increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum and fat malabsorption after omeprazole treatment. The bacterial over-growth consisted of both anaerobes and aerobes with deconjugation ability and was probably associated with an omeprazole induced shift to neutral pH in the gastric juice.
This study was designed to examine further the role of platelet-activating factor (PAF) in asthma, comparing leukotriene B4 (LTB4) release, 5-lipoxygenase activity and intracellular calcium levels ([Ca2+]i) in macrophages. LTB4 and other lipoxygenase metabolites in macrophages in bronchoalveolar lavage fluids obtained from 23 asthmatic patients and 20 control subjects were measured by reverse-phase high-performance liquid chromatography. [Ca2+]i was monitored using the fluorescent probe fura-2. The basal LTB4 release of resting macrophages was not different between groups (0.02+/-0.01 versus 0.05+/-0.02 ng x 10(-6) cells). When stimulated with calcium ionophore A23187 (2.5 microM), however, macrophages from asthmatic patients released more LTB4 than cells from control subjects (30.2+/-3.4 versus 13.7+/-2.1 ng x 10(-6) cells). Although PAF alone did not alter LTB4 release, it enhanced the response to subsequent A23187 stimulation. This effect was noted following short treatment (i.e., 5 min) at concentrations of > or =1.0 microM PAF, with the maximal effect noted after treatment with 5.0 microM PAF + 2.5 microM A23187 (105.1+/-6.7 versus 15.3+/-2.6 ng x 10(-6) cells). Treatment of macrophages with PAF also increased 5-lipoxygenase activity and [Ca2+]i more in cytosols from asthmatic patients than in cytosols from control subjects. These findings support a role of intracellular calcium in the activation of 5-lipoxygenase which, in turn, augments the release of leukotriene B4. Because levels of platelet-activating factor may be increased in the lung during asthma and can increase the subsequent release of a chemotactic mediator leukotriene B4, from macrophages, these findings suggest that platelet-activating factor may prime the constitutive cells of the lung to augment inflammatory effects important in the pathogenesis of asthma.
Association between Ley expression and prognosis of breast cancer was investigated using monoclonal antibody (MoAb) FS01, which recognizes Ley as an epitope, inhibits the procoagulant activity of cancer cell-derived coagulating activity 1 (CCA-1). Expression intensity and procoagulant activity of CCA-1, tissue factor and HLA-DR on breast cancer cell lines were also examined. Immunohistochemical staining of Ley was performed on primary lesions of 223 breast cancer patients who received absolute curative operation. Flow cytometric analysis and clot timer was used to detect expression and activity of each procoagulant on cancer cell lines. The Ley expression was 73.5%, and no significant relation was observed between clinicopathological factors and intensity of Ley expression. The group showing strong Ley positivity had a significantly poorer prognosis than the Ley-negative group in 5-year disease-free survival (p=0.019). Multivariate analysis using the Cox's proportional hazards' regression model showed that Ley expression is an independent prognostic factor (p=0.018), following tumor size and lymph node metastasis. Ley expression on cancer cell surface is higher than tissue factor and HLA-DR. FS01 and anti-tissue factor MoAb inhibited the coagulating activity of tissue factor-expressing lines, but no cells were inhibited by staphylococcal enterotoxin A, which is known to inhibit the coagulating activity of HLA-DR. CCA-1 and tissue factor plays a important role in the blood coagulating activity of breast cancer cell lines. Breast cancer patients are thought to have a poor prognosis because Ley expression on the surface of the cancer cell induces blood coagulation via CCA-1.