Biomedical subjects
Publications and source records attributed to T Fujiwara.
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A 20-year-old man was admitted to our hospital because of an abnormal shadow on chest X-ray Laboratory data revealed a high serum alpha-fetoprotein (AFP) and LDH level. Percutaneous needle biopsy of the tumor suggested primary mediastinal germ cell tumor. Curative resection was performed after three courses of combination chemotherapy (cis-platinum, VP-16, bleomycin and adriamycin). A post-operative histological examination of the mass revealed total necrosis. Post-operative course was uneventful, and he has been free of recurrence for the last six months.
JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a strong and durable ex vivo inhibitory effect on PEP in various regions of the rat brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin, and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0, 4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant increase in ACh release in the frontal cortex and hippocampus of young rats at oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide functions inhibiting PEP, that it activates cholinergic transmission and that it enhances learning and memory.
We report the usefulness of monitoring hepatic venous saturation (ShVO2) during open heart surgery for a patient with severe liver dysfunction. The patient was a 55-year-old man who had been suffering from acute aortic regurgitation due to bacterial endocarditis. Indocyanine green retention test at 15 min was 55%. Serum GOT, GPT and T bilirubin were 56 U.l-1, 35 U.l-1 and 1.5 mg.dl-1 respectively. Aortic valve replacement was scheduled in spite of severe liver dysfunction because amelioration of congestive heart failure after the operation was expected to improve liver dysfunction to the previous chronic state. Anesthesia was induced and maintained by intermittent administration of diazepam and low dose of fentanyl with 100% oxygen. After induction, we inserted a balloon tipped pulmonary catheter with ultra-red beam into hepatic vein by fluoroscopy guidance and monitored ShVO2 as an index of hepatic oxygen supply/demand balance. During re-insertion of a thoracic catheter, we could detect the continued decrease in hepatic vein saturation even after the improvement of systemic circulatory state. Postoperatively, liver function became slightly worse for a short period and improved thereafter. These results suggest that ShVO2 monitoring is clinically useful in detecting hepatic oxygen supply/demand imbalance which circulatory monitoring could not uncover during open heart surgery.
A case of neurinoma from the spinal accessory nerve which is located in the cisterna magna is reported. A 54-year-old woman was admitted to the institute in 1990 with complaints of headache, nausea and ataxic gait for several months. Plain CT showed dilation of the lateral ventricles and a mass of lower density in the cisterna magna. The capsule and septa of the mass were enhanced with contrast medium. MRI showed the mass was low intense on T1-weighted images and high intense on T2-weighted images. Gadolinium visualized the mass multicystic. V-P shunt was performed before tumor resection. Through suboccipital craniectomy and C1 laminectomy the tumor was removed. The tumor had a long neck attached to the right spinal accessory nerve and extended to the cisterna magna.
Measurement of cerebral blood flow and energy metabolism using PET with 15O and 18F labeled tracers allows quantitative evaluation of cerebral metabolism that can be perturbed in pathological states. Neurotransmission is a new target that is visualized by labeling of substrates of enzymes that are involved in neurotransmitter synthesis or degradation. Neuronal receptors are mapped by introducing the labeled ligands that are specifically bound to the receptors in question. We developed unique tracers that label dopamine D2 or histamine H1 receptors. With other available ligands for the muscarinic cholinergic receptors and [18F] fluorodopa, we started clinical investigations to document the state of neurotransmission in patients with epilepsy, Parkinson's disease and dementia. Using [11C] doxepin we observed an increase of H1 receptors in the epileptic foci that showed decreased glucose metabolic rate at the interictal phase. This phenomenon is compatible with reported increase of mu opiate receptors in the brains of epileptic patients. Brain uptake of FDOPA (Ki), calculated by the graphical plot was found relatively stable with age both in the normal population and dementia patients. However, the striatal Ki of FDOPA of severely demented patients significantly reduced, compared with the normal aged subjects. The correlation analysis between FDOPA Ki and severity of dementia as assessed by mini-mental state examination revealed a significant reduction of Ki associated with the disease progression. Increase in D2 receptor density as assessed by the uptake of YM 09151-2 was observed in cases with reduced FDOPA uptake, which may correspond to the state of supersensitivity of the D2 receptors.
99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) is a newly developed liver imaging ligand which specifically binds to asialoglycoprotein receptor on the hepatic cell surface. We investigated whether 99mTc-GSA scintigraphy was able to be used as indexes for the residual functional reserve and the early regeneration of the hepatocyte after the hepatic resection. Four patients with metastatic liver cancer, 3 patients with hepatocellular carcinoma, and 1 patient with cholangiocellular carcinoma were studied. Basically, each patient was examined 4 times (before, 3, 10, 20 days after the operation). Immediately after i.v. injection of 185 MBq (3 mg) of 99mTc-GSA, serial images and dynamic data were obtained. Serial changes of HH15, as an index of blood clearance of the tracer calculated from the uptake ratio of heart at 15 minutes to that at 3 minutes, and LHL15, as an index of hepatic accumulation calculated from the uptake ratio of liver to liver plus heart at 15 minutes after the injection were analyzed before and after hepatectomy. Three out of 4 lobectomy patients which showed increased HH15, and decreased LHL15 as compared with the preoperative data were considered to be decreased residual hepatic functional reserve. The remaining one lobectomy patient showed increased HH15, but increased LHL15 inversely. One patient of two partial resections of hepatocellular carcinoma with liver cirrhosis demonstrated transiently decreased HH15, and increased LHL15. Two patients with metastatic liver cancer (one partial resection, six partial resections) showed decreased HH15, and increased LHL15. Postoperatively increased hepatic accumulation was presumed to be increased functioning hepatocyte or transiently increased asialoglycoprotein receptor on the cell surface by up-regulation. 99mTc-GSA scintigraphy might be helpful for non-invasive method to detect the residual functional reserve and the early regeneration of the hepatocyte after the hepatic resection.
Magnetic resonance cholangiopancreatography (MRCP) is a method that can depict the main pancreatic duct non-invasively; however, its tendency to overestimate ductal stenosis is being noted. The authors used secretin to stimulate the output of pancreatic juice, which increased the signal of the main pancreatic duct and consequently minimized the occurrence of pseudostenosis artifacts in MRCP. MRCP images of 54 patients suspected of having pancreatic disease were visually evaluated by two observers before and after administration of secretin (1 clinical unit/kg). Improved delineation of the main pancreatic duct (68.5-59.3%, p < 0.05) and its side branches (40.7-29.6%, p < 0.05) was obtained with good interobserver agreement (kappa = 0.71-0.68).
To clarify the mechanism of the effect of lansoprazole in the healing of human gastric ulcer, the uptake sites of lansoprazole were studied using endoscopically biopsied specimens from the margin of the gastric ulcer. The specimens were incubated in a medium containing 3H-lansoprazole for 5 or 15 min., postfixed with 1% osmic acid and embedded in Epon. The semithin or ultrathin sections were made and radioautographic emulsion films were applied by the wire-loop method. 30 days after the incubation, the sections were developed, fixed and observed by light and electron microscopy. As a result, the uptake sites of lansoprazole were accumulated on the fibroblasts located near the tip portion of the gastric mucosa and on the unmyelinated nerve fibers as well as on the parietal cells. Some of the uptake sites were also observed near the plasma membrane of the bacteria in the gastric lumen. From these observations, lansoprazole uptake sites were not only on the parietal cells but on the fibroblasts and the bacteria, suggesting that the effect of lansoprazole was exerted partly through the influence on the mesenchymal cells and Helicobacter pylori-related organisms.
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Myocardial perfusion and fatty acid metabolism were assessed by using myocardial single-photon emission computed tomography with thallium and beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) during acute and/or late stages of myocardial infarction in 157 infarcted segments of 100 patients. The incidence of reduced thallium perfusion relative to BMIPP uptake ("T-type" mismatch) was significantly (p < 0.05) lower (9%) compared to that of reduced BMIPP uptake relative to thallium perfusion ("B-type" mismatch) (59%) or non-mismatched segment (32%). In an anteroseptal region, B-type dissociation had a significantly higher incidence compared to no or T-type mismatch; 68% vs. 27% vs. 5%, respectively, whereas the incidence of T-type uptake was relatively high in inferior and posterolateral regions; 13%, 11%, respectively. Severe coronary stenosis was observed in 76% of B-type segments and 72% of non-mismatched segments but in only 43% of T-type segments. The incidence of regional wall motion abnormality was significantly lower (46%) in the T-type mismatch segments when compared to the B-type (91%) or non-mismatched segments (96%). In conclusion, myocardial fatty acid metabolism was more markedly impaired compared to an involved coronary perfusion, resulting in the mismatch of perfusion and fatty acid metabolism. Coronary stenosis and regional wall motion abnormality are more closely related to "B-type" mismatch but not necessarily to "T-type" dissociation, probably because of attenuation artifacts in inferior and posterolateral regions in thallium scan.
In order to make clear how the ultrastructure of the bovine second-passage retinal pigment epithelium (RPE) was affected by exposure to L-dopa and oxygen, we compared the toxic effects of melanotic and amelanotic RPE. The oxygen levels in the incubators and the L-dopa concentrations in the media were adjusted to 10% or 20% oxygen by adding nitrogen gas and 100 microM or 250 microM L-dopa, respectively. After 24 hours, melanotic and amelanotic RPE were fixed and embedded in epon. Ultrathin sections were examined by transmission electron microscopy. Rough endoplasmic reticula were found to be dilated and ribosomes were extinguished in both melanotic and amelanotic RPE. The damage by L-dopa in melanotic RPE was less than that in amelanotic RPE and less in 10% oxygen than in 20% oxygen.
A case of rare thymic squamous cell carcinoma was reported. A 46-year-old female was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest CT showed anterior mediastinal tumor and histological diagnosis of squamous cell carcinoma was made by needle biopsy under CT guide. Esophagus and lung were no abnormal findings, we thought the primary region was thymus. On mid-sternotomy, anterior mediastinal tumor was resected with thymus, right phrenic nerve and pericardium, however it was not direct invasion to heart, great vessels, lung and chest wall. Resection of peripheral fatty tissue and dissection of mediastinal lymph nodes as much as possible, it was not capsular invasion and mediastinal lymph nodes metastasis and complete curative resection was able to perform. Additional radiation therapy was done, post-operative course was uneventful.
Transgenic expression of genes encoding the alpha' and beta subunits of beta-conglycinin, one of the major seed storage proteins of soybean (Glycine max [L.] Merr.), was analyzed in Arabidopsis thaliana (L.) Heynh. under conditions of sulfate deficiency. Temporal patterns of expression of both the intact beta subunit gene and the beta subunit gene promoter fused to the beta-glucuronidase (GUS) gene are similar in soil-less cultures using rockwool, suggesting that the response to sulfate deficiency is regulated mainly at the level of transcription. In hydroponic cultures with various concentrations of sulfate, expression of both the intact beta subunit gene and the beta subunit gene promoter-GUS fusion gene were negatively correlated to increased sulfate concentrations in the culture medium. Transfer of transgenic A. thaliana plants carrying the beta subunit gene promoter-GUS fusion from sulfate-deficient to sulfate-sufficient control medium caused GUS activity in developing siliques to be repressed within two days. A reverse shift, where the plants were transferred from the control to sulfate-deficient medium, caused GUS activity to become higher than that in seeds of the control plants within two days. These results indicate that the expression of the beta subunit gene promoter responds rapidly to changes of sulfate availability.
It has been reported that aprotinin (apr) is effective for hemostasis during and after the extracorporeal circulation (ECC) for cardiac or great vessel surgery. However its mechanism remains still obscure. In this study, we observed relationships between changes in interleukin-8 (IL-8), endothelial factors, or D-dimer and aprotinin administered before and after the ECC. Fourteen patients in whom cardiac or great vessel surgery was done using ECC were divided randomly into two groups. Seven subjects in Group I (G-I) were infused 10(6) KIU of apr immediately after anesthesia, immediately before and after the ECC, respectively, and 10(6) KIU of apr were also added during the ECC. Seven other subjects (G-II) were infused 10(6) KIU of apr immediately before and at three hours after the ECC, and also 2 x 10(6) KIU of apr immediately after the ECC. No marked hemorrhagic tendency was noted in all subjects and increase in plasma D-dimer was not marked. Immediately after the ECC, granulocyte elastase in plasma increased markedly in both groups but subsequently decreased in the G-II alone while it remained unchanged in the G-I. Similar changes were observed in plasma IL-8 values. During the ECC, intercellular adhesion molecule-1 in plasma decreased in both groups but von Willebrand factor activity decreased in the G-I alone. From the above data, the hemostatic effect of apr may contribute to protect the dysfunction of endothelial cells or to enhance recovering from the dysfunction during the ECC.
Two-dimensional solid-state 13C homonuclear and 13C-15N heteronuclear NMR experiments for dipolar correlations between isotropic chemical shifts were performed for adenosine uniformly labeled with 13C and 15N. All the 13C and 15N signals were assigned from the dipolar couplings. In the mixing periods of the experiments, 13C-13C and 13C-15N dipolar interactions under magic angle spinning conditions were recovered by USEME and TEDOR pulses respectively, which are rf multipulse sequences applied synchronously with sample spinning. Dipolar mixing periods were set to times at which only spin pairs connected with direct covalent bonds give rise to cross peaks in the 2-D spectra. Thus, these high resolution spectra unveil a network of 13C and 15N spins connected with covalent bonds in solids. Structural information obtained for adenosine by the 2-D solid-state NMR will be discussed.
OBJECTIVE: To determine whether there is a seasonal variation in blood pressure in hypertensive patients whose daily lifestyle is similar in summer and in winter, and who live almost entirely indoors in a stable environmental temperature. SUBJECTS AND METHODS: During summer and winter, blood pressure was measured by ambulatory blood pressure monitoring in outpatients with essential hypertension, and environmental temperature was measured by electrothermometer while the patients were awake. The 24-h blood pressure data were analysed after being divided into four groups: morning, afternoon, night-time and sleeping periods. RESULTS: We studied 25 outpatients (mean +/- SD age 57 +/- 12 years) who spend virtually the entire day indoors in both summer and winter. Measurements of systolic and diastolic blood pressure in the morning and night-time periods were significantly higher in winter than in summer (differences of 7.5 +/- 14.7 and 4.1 +/- 8.8 mmHg and 8.2 +/- 14.8 and 4.5 +/- 8.1 mmHg, respectively). Blood pressure measured in the afternoon and during sleeping periods did not differ significantly. No correlation was observed between the seasonal change in blood pressure in the morning and that at night. Environmental temperatures were significantly higher in the morning, afternoon and night-time periods during summer than those during winter. The differences among these periods were not statistically significant. CONCLUSIONS: There is a seasonal variation in blood pressure in the morning and night-time periods during winter in hypertensive patients who live essentially indoors in a relatively stable environmental temperature. Pressor factor(s) may differ between morning and night-time periods during winter.