Search PubMed⌕ Search

Biomedical subjects

M Kudo

Publications and source records attributed to M Kudo.

At least 271 records · Page 15Linked to original sources

Des-gamma-carboxy prothrombin (PIVKA-II) and alpha-fetoprotein-producing IIc-type early gastric cancer.

We describe the case of a 56-yr-old man with primary gastric adenocarcinoma, who had an extremely high plasma level of des-gamma-carboxy prothrombin (2.45 AU/ml) and of serum alpha-fetoprotein (2810 ng/ml). Histopathologically, the gastric cancer was a IIc type of early cancer which consisted of a combination of a poorly differentiated adenocarcinoma and a well-differentiated tubular adenocarcinoma. The association of a hepatic tumor including hepatocellular carcinoma or liver metastasis was ruled out by ultrasonography, computed tomography, radiocolloid liver scan, magnetic resonance imaging, and angiography. Foci strongly resembling hepatocellular carcinoma (hepatoid differentiation) were noted in the gastric tumor. Localization of des-gamma-carboxy prothrombin and alpha-fetoprotein within the tumor cells, especially within the hepatoid differentiated foci, was demonstrated by the immunohistochemical staining of tissue obtained at biopsy and the resected specimen. This case seems to be the first case reported in which des-gamma-carboxy prothrombin was produced by the gastric cancer. This finding supports the theory of hepatoid differentiation of a gastric cancer.

Adenocarcinoma↗

Multiple hemangiopericytomas of the spleen.

Splenic tumors are uncommon. Described is a 58-yr-old man with multiple hemangiopericytomas of the spleen. Hemangiopericytoma is categorized as a benign vascular tumor, but has a relatively high malignant potential. A review of the literature shows that the case we present is only the second ever reported of a tumor originating from the spleen. Radiological findings and the treatment of the tumor are discussed.

Hemangiopericytoma↗

[Effects of sevoflurane anesthesia on dopamine metabolism in the rat brain].

To elucidate the mechanism of general anesthesia, effects of sevoflurane anesthesia on dopamine metabolism in rat brain were studied. Sevoflurane 3% was administered for 20 minutes to Wistar male rats weighing 230-270 g under spontaneous respiration. The rats were sacrificed by decapitation and the brains were rapidly removed. They were dissected into nine discrete regions, locus coeruleus, pons plus, medulla oblongata, hypothalamus, thalamus, basal ganglia, midbrain, hippocampus, amygdala and cerebral cortex. The contents of dopamine (DA) and its major metabolites, 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) were measured by high performance liquid chromatography with the dual-cell coulometric detector before anesthesia, 20 minutes after the start of anesthesia and at the recovery from anesthesia. Significant increases in DA levels were observed in the pons, hypothalamus, thalamus and amygdala by sevoflurane anesthesia as compared with the control group. DOPAC levels increased significantly in the pons, hypothalamus, basal ganglia and cerebral cortex at the recovery from anesthesia. A significant increase in HVA levels was observed in amygdala by sevoflurane anesthesia, while an appreciable decrease in HVA levels was observed in hippocampus at recovery from anesthesia. It is concluded that DA metabolism is significantly suppressed in the pons, hypothalamus, thalamus, basal ganglia, midbrain and amygdala during sevoflurane anesthesia and this change in DA metabolism may be associated with the mechanism of sevoflurane anesthesia.

Anesthetics↗

[Pharmacokinetics of ketamine and pentazocine during total intravenous anesthesia with droperidol, pentazocine and ketamine].

Pharmacokinetics was studied in ten surgical patients who underwent various operative procedures of about 4 hours under total intravenous anesthesia with droperidol, pentazocine and ketamine (DPK). Plasma levels of ketamine, its metabolites and pentazocine were determined thirteen times during and after DPK. During anesthesia, ketamine (KO) and norketamine (KMI) levels ranged from 0.7 to 1.0 micrograms.ml-1 and from 0.09 to 0.74 micrograms.ml-1, respectively. A small amount of dehydronorketamine (KM II) was detected only 90 min after the start of DPK anesthesia. Plasma half-lives of ketamine were calculated to be 33 min for distribution phase (alpha phase) and 60 min for elimination phase (beta phase), respectively. Pentazocine levels decreased 300 min after the induction of DPK to 10% of the control level measured 5 min after its injection. Plasma half-lives of pentazocine were 60 min for alpha phase and 140 min for beta phase, respectively. The data obtained in this clinical study show that pharmacokinetics of ketamine during DPK is almost similar to that of DFK.

Adolescent↗

[Clinical utility of receptor imaging in the assessment of liver function].

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

Adult↗

[A case of ruptured aortic arch aneurysm into the lung].

Successful surgical treatment of aortic arch aneurysm ruptured into the left lung was reported. The patient was a 74-year-old man suffering from recurrent hemoptysis. Computed tomography and aortic angiography demonstrated a giant aortic arch aneurysm. Emergency operation was performed. Arch reconstruction by a Dacron graft was performed with hypothermic circulatory arrest. The post operative course was uneventful and there was no evidence of cerebral complication. In the emergency operation for ruptured aortic arch aneurysm, hypothermic circulatory is very useful method for cerebral protection.

Aged↗

[Phase III multi-center clinical study on 99mTc-GSA, a new agent for functional imaging of the liver].

A multi-center clinical study was performed in patients with hepatic disorders to evaluate the clinical usefulness of 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to asialoglycoprotein receptors on hepatocytes. The blood clearance and hepatic accumulation were evaluated on the basis of the dynamic data and serial hepatic images obtained for 20 min after 99mTc-GSA injection. The blood clearance and hepatic accumulation indices of 99mTc-GSA demonstrated the followings. 1) In acute liver diseases, these indices reflected the clinical features of the disease and correlated with the laboratory test indices for the blood coagulation system. 2) In chronic liver diseases, these indices changed in direct proportion to the progression of the hepatic disorder and correlated well with the conventional laboratory test results. 3) In obstructive jaundice, these indices aided evaluation of the liver function despite the high serum bilirubin level. 4) The indices reflected the change in the number of hepatocytes before and after hepatectomy. The scintigraphic findings with 99mTc-GSA permitted both functional and morphological evaluations of the liver and provide additional information compared with conventional liver scintigraphy. These results suggest that 99mTc-GSA scintigraphy may be useful for evaluating both the function and morphology of the liver from a new viewpoint of receptor-mediated accumulation.

Drug Evaluation↗

[Hepatic receptor imaging with Tc-99m GSA: estimates of liver function in acute liver disease].

Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.

Acute Disease↗

[Phase II clinical study on 99mTc-GSA, a new agent for functional imaging of the liver].

Phase II study of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes, was performed in 81 patients with liver diseases to validate its safety and possibility for the evaluation of hepatic function. None of adverse reactions, abnormal clinical laboratory findings and anti-99mTc-GSA antibody production due to 99mTc-GSA was recognized. Immediately after the injection of 99mTc-GSA, the dynamic data and serial hepatic images were obtained for 60 min. The indices for blood clearance and liver accumulation were calculated based on the counts in the regions of interest on the hearts and livers. In 54 patients with chronic hepatic disorders such as liver cirrhosis, the blood clearance and liver accumulation of 99mTc-GSA were retarded according to the progress of the hepatic disorders. The findings of 99mTc-GSA scintigraphy also reflected the hepatic functions of the patients with large hepatic tumors, obstructive jaundice and acute hepatitis. These results suggest that 99mTc-GSA has the clinical potentials to evaluate the liver functions in the patients with hepatic disorders.

Adult↗

[Extended aortic reconstruction for dissecting aneurysm of the aorta].

While lifesaving palliative surgery may be selected for dissecting aneurysm of the aorta, extended reconstructive surgery has been advocated as a more curative procedure. We performed a variety of extended reconstructive surgeries, for example, replacement of the ascending aorta and the aortic arch, subtotal replacement of the thoracic aorta, replacement of the entire descending thoracic aorta and replacement of the entire descending aorta in 20 cases of dissecting aneurysm of the aorta. However, the operative mortality remained high as 35%, and the operative procedures have not yet to be standardized. We believe that it is extremely important to strive for much greater improvement in the operative results by correct selection of the operative indications, and by improving the operative techniques and patient management during surgery.

Adult↗

Receptor index via hepatic asialoglycoprotein receptor imaging: correlation with chronic hepatocellular damage.

Galactosyl human serum albumin is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. The receptor-binding agent was synthesized by the covalent coupling of carbohydrate units to human serum albumin. The clinical utility of technetium-99m-labeled galactosyl human serum albumin was evaluated in six control subjects with normal livers and in 50 patients with chronic liver disease. The parameter, receptor index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus the heart at 15 min after the intravenous injection of 3 mg of labeled ligand. Values for the receptor index in the control subjects and in patients with mild, moderate, and severe liver disease were 0.936 +/- 0.015, 0.909 +/- 0.034, 0.848 +/- 0.070, and 0.669 +/- 0.085, respectively. Good correlations were obtained between the receptor index and conventional liver function tests, such as the Child-Turcotte criteria score (rs = -0.776, p = 0.0001), prothrombin time (r = 0.736, p = 0.0001), and the plasma disappearance rate of indocyanine green (r = 0.805, p = 0.0001). These significantly high correlations of the receptor index with classical indicators of hepatic functional reserve suggest that the receptor index is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

Adult↗

Mutational activation of c-Ha-ras gene in squamous cell carcinomas of rat Zymbal gland induced by carcinogenic heterocyclic amines.

The activation of the c-Ha-ras gene and its carcinogen specificity were examined in squamous cell carcinomas (SCCs) induced by the mutagenic heterocyclic amines 2-amino-3-methylimidazo [4,5-f]quinoline (IQ),2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in the Zymbal gland in rats. DNA fragments of the c-Ha-ras gene were amplified from formalin-fixed and paraffin-embedded tissues by polymerase chain reaction and analyzed for activating mutations involving codons 12, 13, and 61 by oligonucleotide differential hybridization and sequencing. c-Ha-ras mutations were found in four of seven and two of six Zymbal gland SCCs induced by IQ and MeIQx, respectively. These mutations were located in either codon 13 or 61. In the case of MeIQ, point mutations at the second nucleotide of codon 13 were found in nine of the total 14 Zymbal gland SCCs and in one papilloma. Of the nine SCCs that had mutations in codon 13, two possessed mutations at the second nucleotide of codon 12 as well. Most reported mutations in c-Ha-ras are located at codon 12 or 61, but the heterocyclic amines in this study induced mutations not only at codons 12 and 61 but also in codon 13. Transversions were the dominant mutation induced by these heterocyclic amines.

Animals↗

Malignant choroid plexus papilloma of the IV ventricle.

We report a case of malignant choroid plexus papilloma (MCPP) of the IV ventricle in a child with prominent extraventricular expansive growth, mostly into the cerebellopontine angle. Interestingly enough, the tumor was entirely covered by thin, smooth, membranous, fibrous tissue, probably derived from the pia mater. In addition, hydrocephalus was not observed. The reason for the lack of hydrocephalus remains speculative, but it is possible that the presence of pure, nonexpansive, fibrous covering on the tumor might have suppressed the tumor growth to some extent, resulting in progressively increased intratumoral pressure. This, in turn, caused the suppression of excessive cerebrospinal fluid production by the tumor cells. From the diagnostic standpoint, immunohistochemical studies, using antiepithelial membrane antigen (EMA) and antitissue polypeptide antigen (TPA), were demonstrated to be useful for diagnosing the tumor.

Cerebral Ventricle Neoplasms↗

Functional hepatic imaging with receptor-binding radiopharmaceutical: clinical potential as a measure of functioning hepatocyte mass.

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means +/- standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933 +/- 0.006, 0.789 +/- 0.045, 0.723 +/- 0.033, and 0.488 +/- 0.094, respectively. The difference between the mean values of each group was statistically significant (P less than 0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.

Asialoglycoprotein Receptor↗

Human ubiquitin-activating enzyme (E1): compensation for heat-labile mouse E1 and its gene localization on the X chromosome.

We have constructed interspecific somatic cell hybrids between a temperature-sensitive (ts) mutant cell line of mouse FM3A cells, ts85, that has a heat-labile ubiquitin-activating enzyme (E1) and a human diploid fibroblast cell line, IMR-90. A hybrid clone that could grow stably at a nonpermissive temperature (39 degrees C) was obtained. Segregation of the hybrid cells at a permissive temperature (33 degrees C) gave rise to temperature-sensitive clones. The electrophoresis of extracted histones and karyotype analysis of the segregants revealed a close correlation of the ability to grow at 39 degrees C, the presence of uH2A (ubiquitin-H2A semihistone) at 39 degrees C, and the presence of the human X chromosome. One of the hybrid clones that could grow at the nonpermissive temperature contained the X chromosome as the only human chromosome. The sodium dodecyl sulfate-polyacrylamide gel electrophoretic pattern of affinity-purified E1 showed that this hybrid clone contained both human and mouse type E1. Thus we conclude that the functional gene for human E1 is located on the X chromosome.

Animals↗

Hepatic uptake of [99mTc]galactosyl-neoglycoalbumin is sensitive to receptor quantity.

[Technetium-99m]galactosyl-neoglycoalbumin (TcNGA) is a synthetic radioligand specific to the receptor, hepatic binding protein (HBP), which resides exclusively at the cell surface of hepatocytes. If the TcNGA time-activity data are to provide valid estimates of receptor biochemistry via pharmacokinetic modeling, the shape of the hepatic uptake curve must change with alterations in receptor concentration or affinity. An index of TcNGA hepatic uptake, T90, was obtained by calculating the time at which the liver time-activity curve reached 90% of its maximum. Receptor quantity was measured by Scatchard binding assay of liver biopsy samples obtained prior to each TcNGA study. The range of T90 was 3.7-16.8 min; HBP quantity ranged from 0.022 to 0.100 mumol. Significant correlation (r) and slope (b) was observed between T90 and HBP quantity (r = 0.82, P = 0.003; tb = 3.98, P = 0.003). We concluded that the hepatic uptake of TcNGA is sensitive to HBP quantity.

Adult↗