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Biomedical subjects

K Kumada

Publications and source records attributed to K Kumada.

At least 37 records · Page 2Linked to original sources

[Neuromonitoring of acute internal carotid artery occlusion].

We experienced a patient with acute thrombosis of the unilateral internal carotid artery. We monitored the brain tissue temperature and intracranial pressure not only in both hemispheres simultaneously but also continuously throughout the process of brain death. The patient was a 73-year-old male who presented to our emergency room with right hemiparesis and aphasia. On admission to our department, no specific pathological findings were identified by brain CT. However a following investigation with left carotid arteriogram demonstrated a complete occlusion of the left internal carotid artery. Probes to monitor intraparenchymal temperature (Tip) and intracranial pressure(ICP) were inserted surgically into the bilateral hemispheres, and these two parameters were monitored continuously until the patient's death. Initially, Tip in the infarcted hemisphere was lower than that in the intact hemisphere, and the left hemisphere's ICP was significantly higher than that of the right one. When the ICP in the left hemisphere exceeded 40 mmHg, bilateral ICPs became equal. Brain herniation was confirmed when the ICP became progressively elevated thereafter. Subsequently the bilateral Tips became equal and lower than the bladder temperature following the brain herniation. In this case, we successfully monitored two parameters while the patient was in the process of brain death; i.e., brain ischemia, complete loss of brain circulation and subsequent decrease in the brain tissue temperature.

Acute Disease↗

[Optimal dosage of UFT in a weekday-on/weekend-off schedule as a postoperative adjuvant chemotherapy for colorectal cancer].

In evaluations of adjuvant chemotherapy with oral anticancer agents, compliance in taking the drug as prescribed (compliance), adverse reactions, and feasibility are important factors in setting the dose. A weekday-on/weekend-off schedule, in which 600 mg/day of UFT was taken for 5 consecutive days and not taken on the following 2 days, was carried out as a postoperative adjuvant chemotherapy for one year in 87 patients with colorectal cancer who had undergone potentially curative resection. The prescribed dose and the dose of ingestion confirmed by physician interview were both highly consistent with the dose of ingestion according to the patients' self reports, with consistency rates of more than 94% for both. Relative performance (RP) yielded a value of 0.72, and individual dose intensity (IDI) yielded 0.8 on average. Female gender, low body weight, and low body surface area were factors that negatively affected feasibility. None of the adverse reactions was serious. Based on the feasibility and adverse reactions, the dosage of UFT should be set according to the body surface area at 375-425 mg/m2/day. When this schedule is used as one arm of a controlled study, it is suggested that the dose should be decided with 400 mg/m2 as a guideline.

Adult↗

Control of metaphase-anaphase progression by proteolysis: cyclosome function regulated by the protein kinase A pathway, ubiquitination and localization.

Ubiquitin-mediated proteolysis is fundamental to cell cycle progression. In the fission yeast Schizosaccharomyces pombe, a mitotic cyclin (Cdc13), a key cell cycle regulator, is degraded for exiting mitosis, while Cut2 has to be destroyed for the onset of sister chromatid separation in anaphase. Ubiquitination of these proteins requires the special destruction box (DB) sequences locating in their N-termini and the large, 20S complex called the anaphase-promoting complex or cyclosome. Here we show that cyclosome function during metaphase-anaphase progression is regulated by the protein kinase A (PKA) inactivation pathway, ubiquitination of the cyclosome subunit, and cellular localization of the target substrates. Evidence is provided that the cyclosome plays pleiotropic roles in the cell cycle: mutations in the subunit genes show a common anaphase defect, but subunit-specific phenotypes such as in G1/S or G2/M transition, septation and cytokinesis, stress response and heavy metal sensitivity, are additionally produced, suggesting that different subunits take distinct parts of complex cyclosome functions. Inactivation of PKA is important for the activation of the cyclosome for promoting anaphase, perhaps through dephosphorylation of the subunits such as Cut9 (Apc6). Cut4 (Apc1), the largest subunit, plays an essential role in the assembly and functional regulation of the cyclosome in response to cell cycle arrest and stresses. Cut4 is highly modified, probably by ubiquitination, when it is not assembled into the 20S cyclosome. Sds23 is implicated in DB-mediated ubiquitination possibly through regulating de-ubiquitination, while Cut8 is necessary for efficient proteolysis of Cdc13 and Cut2 coupled with cytokinesis. Unexpectedly, the timing of proteolysis is dependent on cellular localization of the substrate. Cdc13 enriched along the spindle disappears first, followed by decay of the nuclear signal, whereas Cut2 in the nucleus disappears first, followed by decline in the spindle signal during metaphase-anaphase progression.

Anaphase↗

The effect of flow on the neutrophil-mediated Ca2+ responses in human vascular endothelial cells stimulated by endotoxin.

Leukocyte-vascular endothelial cell (EC) interactions which promote inflammatory and immune reactions involve bidirectional signaling between two cell types. We investigated the effects of flow on neutrophil-mediated changes in endothelial intracellular Ca2+ levels ([Ca2+]i). Cultured human umbilical vein ECs stimulated by endotoxin were labeled with Fura-2 and exposed to fluid flow with neutrophils. The individual changes in [Ca2+]i were monitored. The application of flow with neutrophils to stimulated ECs led to an increase in [Ca2+]i although either flow without neutrophils or neutrophils without flow rarely induced a rise in [Ca2+]i. Furthermore, flow application with neutrophils to unstimulated ECs also rarely promoted a rise in [Ca2+]i. These findings suggest that the flow might thus induce or enhance the inflammatory process by the induction of Ca2+ signaling in endotoxin-stimulated endothelium facing neutrophils in the blood flow.

Calcium↗

Spontaneous rupture of a nonparasitic liver cyst complicated by intracystic hemorrhage.

a case of spontaneous rupture of simple liver cyst complicated by intracystic hemorrhage is described. This rare condition was detected in a 61-year-old man who underwent left trisegmentectomy of liver under a suspected diagnosis of cystadenocarcinoma because of elevated serum levels of carbohydrate antigen (CA) 19-9 and DUPAN 2, and the presence of an intracystic structure. The resected specimen showed a benign liver cyst with intracystic hematoma and high levels of CA19-9 and DUPAN 2 in the cystic fluid. It is suggested that cyst rupture may increase serum levels of tumor markers whose levels are high in the cystic fluid, and that repeated observations of an intracystic structure may be the most reliable method to distinguish intracystic hemorrhage from cystic neoplasm.

Antigens, Neoplasm↗

Liver scintigraphy is useful for selecting candidates for preoperative transarterial chemoembolization among patients with hepatocellular carcinoma and chronic liver disease.

BACKGROUND: The indications for preoperative hepatic transarterial chemoembolization (TACE) have not been clarified by recent studies in patients with hepatocellular carcinoma (HCC) complicated by chronic liver diseases. The aim of the present study was to investigate which patients benefit most from preoperative TACE on the basis of hepatic functional reserve. Technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) liver scintigraphy was used to assess hepatic functional reserve before and after TACE. PATIENTS AND METHODS: Liver scintigraphy was performed before and several weeks after TACE in 64 patients with HCC complicated by chronic hepatitis or cirrhosis. The ratio of liver to heart-plus-liver radioactivity of Tc-GSA 15 minutes after injection (LHL15) was calculated. Conventional hepatic functional tests were also performed. Whether to perform hepatectomy after TACE was decided mainly on the basis of the previously reported value of LHL15 > or =0.91. RESULTS: LHL15, prothrombin time, and serum concentration of cholinesterase significantly decreased after TACE in patients with LHL15 > or =20.91 (P <0.01, P <0.05, and P <0.05, respectively). In patients with LHL15 <0.91, LHL15 and functional liver volume significantly increased after TACE (both P <0.05). Eight patients with LHL15 > or =0.91 did not undergo hepatectomy because LHL15 decreased to less than 0.91 after TACE, whereas 7 patients with LHL15 <0.91 underwent hepatectomy because LHL15 increased to more than 0.91 after TACE. Three major postoperative complications occurred in patients with LHL15 > or =0.91, and no major complications occurred in patients with LHL15 <0.91. CONCLUSIONS: The results suggest that preoperative TACE should be performed in HCC patients only when LHL15 is less than 0.91, and that preoperative TACE is not an appropriate treatment for patients with LHL15 > or =0.91 when HCC is resectable.

Adult↗

Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin-activated vascular endothelial cells.

Effects of heparin-like glycosaminoglycans (h-GAGs) on neutrophil adhesion to endothelial cells (ECs) were investigated under physiological flow conditions using human umbilical vein ECs. Neutrophil adhesion to lipopolysaccharide-activated ECs was assayed under rotating conditions with addition of h-GAGs or monoclonal antibodies (mAbs) against selectins. Neutrophil adhesion to activated ECs under rotating conditions was suppressed completely by anti-E-selectin mAb and partially by anti-L-selectin mAb. Addition of dextran sulfate or heparin also significantly inhibited neutrophil adhesion to ECs under the same conditions. Moreover, effects of h-GAGs on neutrophil adhesion to recombinant E-selectin-coated plates were analyzed. Anti-E-selectin mAb and dextran sulfate, but not heparin, significantly inhibited neutrophil adhesion to E-selectin-coated plates. Results suggest that dextran sulfate inhibited E-selectin-mediated neutrophil adhesion to endotoxin-activated ECs under physiologic flow conditions.

Antibodies, Monoclonal↗

Fission yeast APC/cyclosome subunits, Cut20/Apc4 and Cut23/Apc8, in regulating metaphase-anaphase progression and cellular stress responses.

BACKGROUND: The 20S cyclosome/APC complex promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor Cut2/Pds1/securin. The complex has been shown to contain more than 10 proteins in budding yeast and frog. In fission yeast, however, only five (Cut4, Cut9, Nuc2, Apc10, Hcn1) have been identified. RESULTS: More than five hundred temperature-sensitive mutants were screened for identifying those defective in mitotic anaphase. Fifty-five showed the cut (cell untimely torn) phenotype or metaphase-arrest phenotypes, 27 of them locating at new loci. Their extracts were run in sucrose gradient centrifugation, and four showed alterations in the sedimentation profiles. The gene products of cut20+ and cut23+ were thus identified. Phenotypes of cut20-100 mutant highly resemble cut4-533 in many ways: they are hypersensitive to canavanine and CdCl2, and suppressed by PKA-inactivating regulators, cAMP-dependent phosphodiesterase and PKA regulatory subunits. Cut20 interacts closely with Cut4 in the assembly process of cyclosome. But cut20 mutant differs from cut4, as a novel gene stw1+ suppresses cut20 mutant but not cut4. cut23-194 mutant cells are sterile and blocked at metaphase, but does not show sensitivity to the stress and cAMP. TPR repeat-containing Cut23 may not be the stable component of APC/cyclosome, and its level significantly fluctuates during cell cycle. Cut23 may be ubiquitinated and degraded in a cell cycle dependent fashion. CONCLUSIONS: We identified two new subunits of fission yeast cyclosome/APC complex. Our observations indicate that cyclosome components are divided into several subgroups with distinctly different roles.

Adenomatous Polyposis Coli Protein↗

[Sepsis due to Salmonella Oranienburg--a case report].

A previously healthy 15-year-old female was admitted to our hospital complaining of nausea and vomiting. She did not complain of diarrhea. A physical examination revealed a lower right quadrant abdominal tenderness without rebound or spontaneous pain and a knocking pain of the costovertebral angle. A high fever, knocking pain of costovertebral angle, and urinary findings including Gram's stain, lead us to suspect a urinary tract infection, cefotiam was administered intravenously. Spiking fever with shaking chills continued for three days, and three sets of blood cultures were positive for Salmonella Oranienburg, but her urine culture was negative. Her history was taken again, revealing an intake of a processed squid product. The product was confirmed by the local public health center to be Salmonella Oranienburg. Finally food poisoning by Salmonella Oranienburg with sepsis was diagnosed. With cefotiam she became better and was discharged from the hospital on the 10th hospital day. During admission to the hospital she did not experience any diarrhea, and her stool culture was negative. Epidemics of Salmonella Oranienburg food poisoning are relatively rare in the literature. In Japan, one has arisen as a result of contamination of a processed squid product in March 1999. However, there have been no cases without so-called gastroenteritic symptoms (abdominal pain and diarrhea) who were previously healthy and developed sepsis caused by Salmonella Oranienburg, reported in Japan. Even in previously healthy patients, with an epidemic situation of non-typhoidal salmonellosis, salmonella sepsis must be ruled out. Among such cases, those who present with spiking fever and shaking chills should be given antibiotic therapy after taking appropriate cultures.

Adolescent↗

Prevention of reactive oxygen-induced endothelial cell injury by blocking its process.

Endothelial cell (EC) injury induced by reactive oxygen species (ROS) was investigated and effects of Ca(2+) channel blockers, agents which elevate intracellular cAMP levels ([cAMP](i)), and protein kinase inhibitors on H(2)O(2)-induced EC injury were analyzed using human umbilical vein EC cultures. Exposure to H(2)O(2) increased intracellular Ca(2+) levels and decreased [cAMP](i). Ca(2+) channel blockers, [cAMP](i)-elevating agents, and protein kinase inhibitors significantly inhibited H(2)O(2)-induced EC injury. Data suggest that H(2)O(2)-induced EC injury is mediated by extracellular Ca(2+) influx, intracellular cAMP efflux, and intracellular signaling, each of which is blocked by Ca(2+) channel blockers, [cAMP](i)-elevating agents, or protein kinase inhibitors. It is suggested that ischemia/reperfusion injury induced by ROS may be prevented by Ca(2+) channel blockers, [cAMP](i)-elevating agents, and protein kinase inhibitors.

1-Methyl-3-isobutylxanthine↗

Perioperative hepatic functional risk assessed with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin liver scintigraphy in patients undergoing pancreaticoduodenectomy complicated by obstructive jaundice.

CONCLUSION: Liver scintigraphy with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) can be used to predict outcome of biliary drainage and hepatic function after pancreaticoduodenectomy in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. BACKGROUND: Preoperative obstructive jaundice has been reported as a crucial risk factor for serious postoperative complications in patients undergoing pancreaticoduodenectomy. The aim of the present study was to investigate whether Tc-GSA liver scintigraphy can assess hepatic functional risk in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. METHODS: Liver scintigraphy was performed before biliary drainage in 18 patients with obstructive jaundice. The maximum removal rate of Tc-GSA (GSA-Rmax; standard normal value > or = 0.60) was calculated. These patients underwent pancreaticoduodenectomy with wide lymphadenectomy. The efficacy of preoperative biliary drainage was assessed with the decrease in serum bilirubin concentration in the first week after biliary drainage. Postoperative liver function was assessed with the increase in serum bilirubin concentration, which was the difference between the immediate preoperative and maximal postoperative bilirubin concentrations. RESULTS: Serum bilirubin decreased more in the first week after biliary drainage in patients with GSA-Rmax > or = 0.60 (7.64 +/- 1.09 mg/Dl/wk) than in patients with GSA-Rmax < 0.60 (3.56 +/- 1.25 mg/DL/wk, p = 0.042). Postoperative bilirubin increased less in patients with GSA-Rmax > or = 0.60 (0.81 +/- 0.30 mg/dL) than in patients with GSA-Rmax < 0.60 (4.00 +/- 0.69 mg/DL, p = 0.0012). Multivariate analysis showed that GSA-Rmax significantly predicted the postoperative bilirubin increase (p = 0.020).

Adult↗

Cut1 is loaded onto the spindle by binding to Cut2 and promotes anaphase spindle movement upon Cut2 proteolysis.

BACKGROUND: The Cut1 and Cut2 proteins of the fission yeast Schizosaccharomyces pombe form a complex and are required for the separation of sister chromatids during anaphase. Polyubiquitinated Cut2 degrades at the onset of anaphase and this degradation, like that of mitotic cyclin, is dependent on the anaphase-promoting complex/cyclosome. Expression of Cut2 that cannot be degraded blocks sister chromatid separation and anaphase spindle elongation. Here, we have investigated the role of the Cut1-Cut2 interaction in sister chromatid separation. RESULTS: The carboxyl terminus of Cut2 interacts with the amino terminus of Cut1, and temperature-sensitive Cut2 mutants expressed Cut2 proteins that contain substitutions in the carboxyl terminus and fail to interact with Cut1, resulting in aberrant anaphase. Localization of Cut1 alters dramatically during the cell cycle. Cut1 is retained in the cytoplasm during interphase and moves to the mitotic spindle pole bodies and the spindle upon entry into prophase, when spindles are formed. The association between Cut2 and Cut1 is needed for the localization of Cut1 to the spindles, as Cut1 remains unbound to the spindle if complex formation is impaired. Cut2 degrades during anaphase, but Cut1 remains bound to the anaphase spindle. This association with the anaphase spindle requires the conserved carboxyl terminus of Cut1. CONCLUSIONS: Complex formation between Cut1 and Cut2 is needed for the onset of normal anaphase. Cut2 is required for loading Cut1 onto the spindle at prophase and Cut2 proteolysis is needed for the active participation of Cut1 in sister chromatid separation.

Anaphase↗

Trapidil effects on intimal thickening and mRNA levels for platelet-derived growth factor A in human saphenous vein smooth muscle cells.

BACKGROUND: Platelet-derived growth factor (PDGF) A chain, basic fibroblast growth factor (bFGF), and tissue-type plasminogen activator (tPA) from smooth muscle cells (SMCs) have been postulated to initiate SMC proliferation and migration in the process of intimal thickening. OBJECTIVE: In this study we tested whether trapidil, which is reported to reduce intimal thickening, would suppress mRNA increases for all or only some of these genes in human SMC. METHODS: Cultured human saphenous vein SMCs made quiescent by 72-hour incubation in 0.5% serum were stimulated with 3U/mL alpha-thrombin +/- trapidil. Changes in mRNA transcript levels were analyzed by Northern blot. RESULTS: Trapidil decreased thrombin-induced mRNA levels for bFGF and appeared to decrease mRNA for PDGF-A chain, but not for tPA. CONCLUSION: These results suggest that trapidil may reduce intimal thickening at least partly via the suppression of increased bFGF and PDGF-A chain mRNA levels in vascular SMCs.

Autoradiography↗

Endoscopic sphincterotomy and laparoscopic cholecystectomy in an infant with cholecysto-choledocholithiasis.

Laparoscopic cholecystectomy (LC) and endoscopic sphincterotomy (EST) are widely accepted procedures for cholecysto-choledocholithiasis in adults. However, their use in infants has not been reported. An 8-month-old girl presented with high fever and obstructive jaundice. Ultrasound scan showed acute cholecystitis with stones in the bile duct. After 2-week-long antibiotic therapy the acute cholecystitis and hepatic impairment resolved. An endoscopic retrograde cholangiopancreatography (ERCP) confirmed choledocholithiasis and cholecystolithiasis. Risk factors for the development of biliary calculi were not detected. One month after the restoration of her liver function, she underwent EST using a side-viewing endoscope with a small sphincterotome. A common bile duct stone was extracted using a basket catheter. LC was then carried out. The time interval between the EST and LC was 34 days. No complications have been noted for 6 months.

Cholangiopancreatography, Endoscopic Retrograde↗