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Biomedical subjects

T Kashima

Publications and source records attributed to T Kashima.

At least 19 recordsLinked to original sources

Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma.

AIMS: Glypican 3 (GPC3) is a cell surface heparan sulphate proteoglycan expressed specifically in the fetal liver and malignant neoplasms of hepatocyte lineage. The aim was to evaluate the significance of GPC3 in alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) and other forms of GC. METHODS AND RESULTS: We immunohistochemically evaluated GPC3 expression in representative cases of AFP-producing GC and in a tissue microarray of a consecutive series of GCs with other markers of hepatocyte lineage (AFP, PIVKA-II and hepatocyte antigen, HEP). In a series of 10 cases of AFP-producing GC, we observed immunohistochemical positivity for GPC3, PIVKA-II and HEP in 10, three and three cases in components with a hepatoid pattern and in nine, two and five cases in components with a non-hepatoid pattern, respectively. In a series of 118 cases of GC, we observed positivity for AFP, GPC3, PIVKA-II and HEP in one (0.8%), four (3.4%), six (5.1%) and 26 cases (22%), respectively. GPC3 was observed concurrently with AFP and discordantly with PIVKA-II and HEP. GPC3 positivity was clearly stronger in a larger area compared with immunoreactivity for AFP. CONCLUSIONS: GPC3 is a sensitive marker for AFP-producing GC and its hepatoid component and is therefore useful to identify this aggressive subgroup of GC.

Adenocarcinoma↗

Sonographic features of hepatic artery calcification in chronic renal failure.

PURPOSE: Little is known about radiological aspects of hepatic artery calcification. For this reason, the sonographic features of calcified hepatic arteries were studied in patients with chronic renal failure who frequently develop tissue calcification due to hyperparathyroidism. MATERIAL AND METHODS: Ultrasound was performed in 314 patients on dialysis who underwent examination of the liver, spleen and kidney twice in the past 4 years and were reevaluated with particular attention to acoustic shadowing. Abdominal CT was carried out in 219 of these 314 patients, and ultrasound findings were reevaluated with reference to CT findings. RESULTS: A large acoustic shadow was seen in the hilum that corresponded to the calcified hepatic artery on CT in 8 patients, and in another 9, a similar large shadow was seen in the hilum without CT confirmation. Acoustic shadows of various sizes were definitely or most likely due to arterial calcification within the liver in 36 patients. The strength of shadow depended on the angle at which the ultrasound beam hit the artery. Probable calcification of small arteries accompanying portal veins was seen in 70 patients. These changes are different from those due to pneumobilia and biliary tract diseases. CONCLUSION: Calcification of the hepatic artery can be identified by its acoustic shadow.

Aged↗

The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis. An autopsy-based retrospective study of 48 patients.

To evaluate the diagnostic value of a halo on computed tomography (CT) in the diagnosis of invasive pulmonary aspergillosis (IPA), we retrospectively reviewed chest CT scans and autopsy reports for patients who had been admitted to our hospitals for the treatment of hematological malignancy. Pulmonary complications were suspected in all patients and chest CT scans were taken within a month of death. We examined the association between autopsy and CT findings in 48 patients who were diagnosed as IPA (n = 17), candidosis (n = 4), zygomycosis (n = 2), infiltration of hematological malignancy (n = 12), bacterial pneumonia (n = 6), cytomegalovirus pneumonia (n = 2), pulmonary hemorrhage (n = 2), or pulmonary congestion (n = 1). Patients with IPA showed a variety of CT findings, including halo (n = 13), nodules (n = 14), granular shadows (n = 3), masses (n = 6), consolidations (n = 9), wedge-shaped consolidations (n = 1), and cavitation (n = 2). In contrast, 0, 11 and two of the 31 patients without IPA showed halo, nodules and masses, respectively. These signs were more frequently observed in IPA patients than in non-IPA patients. The CT halo, especially, seemed to be specific for IPA in hospitalized neutropenic patients with hematological malignancies who developed antibiotic-resistant fever. For CT findings other than these three signs, there were no significant differences between IPA- and non-IPA patients.

Adolescent↗

Clinical significance of extra-pulmonary involvement of invasive aspergillosis: a retrospective autopsy-based study of 107 patients.

Disseminated aspergillus infection has a poor prognosis, but few reports have been published on extra-pulmonary involvement in aspergillosis. We reviewed 107 autopsy records of patients with invasive aspergillosis. Fifty-five patients had extra-pulmonary aspergillosis. Organs involved included heart, kidney, central nervous system, gastrointestinal tract, spleen, liver, thyroid gland and pancreas. Extra-pulmonary aspergillosis produces different manifestations according to involved organs. Risk factors associated with dissemination included cytotoxic chemotherapy within a month of death (P=0.0087). Lack of response to empiric or preemptive treatment of amphotericin B predicted IA dissemination (P=0.0328). To improve prognosis of IA, it is important to recognize clinical features of extra-pulmonary aspergillosis and to institute the aggressive anti-fungal treatment.

Adult↗

Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis.

We developed a new quantitative system for diagnosis of invasive pulmonary aspergillosis (IPA) using real-time automated polymerase chain reaction (PCR). Intra-assay and interassay precision rates for in vitro examination were 2.53% and 2.20%, respectively, and the linearity of this assay was obtained when there were >20 copies/well. We examined 323 samples taken from 122 patients with hematological malignancies, including 33 patients with IPA and 89 control patients. Blood samples were subjected to PCR antigen detection methods, using enzyme-linked immunosorbent assay (ELISA) and determination of plasma (1-->3)-beta-D-glucan (BDG) concentration. The sensitivities of PCR, ELISA, and BDG measurement for diagnosis of IPA were 79%, 58%, and 67%, respectively; the specificities were 92%, 97%, and 84%. Positive findings on PCR preceded those of computed tomography by -0.3+/-6.6 days, those of BDG measurement by 6.5+/-4.9 days, and those of ELISA by 2.8+/-4.1 days. Real-time PCR was sensitive for IPA diagnosis, and quantitation was accurate.

Adolescent↗

Analysis of a muscular control system in human movements.

In this work, we have studied a muscular control system under experimental conditions for analyzing the dynamic behavior of individual muscles and theoretical considerations for elucidating its control strategy. Movement of human limbs is achieved by joint torques and each torque is specified as the sum of torques generated by muscle forces. The behavior of individual muscles is controlled by the neural input which is estimated by means of an electromyogram (EMG). In this study, the EMGs for a flexor and an extensor are measured in elbow joint movements and the dynamic behavior of individual muscles is analyzed. As a result, it is verified that both a flexor and an extensor are activated throughout the entire movement and that the activation of muscles is controlled above a specific limit independent of the hand-held load. Subsequently, a system model for simulating elbow joint movements is developed which includes the muscle dynamic relationship between the neural input and the isometric force. The minimum limit of muscle activation that has been confirmed in experiments is provided as a constraint of the neural input and the criterion is defined by a derivative of the isometric force of individual muscles. The optimal trajectories formulated under these conditions are quantitatively compared with the experimentally observed trajectories, and the control strategy of a muscular control system is studied. Finally, a muscular control system in multi-joint arm movements is discussed with regard to the comparative analysis between observed and optimal trajectories.

Animals↗

Developmental changes in pharmacokinetics and pharmacodynamics of warfarin enantiomers in Japanese children.

OBJECTIVE: To clarify developmental changes in the pharmacokinetics and dynamics of warfarin enantiomers to establish rational pediatric dosage. METHODS: Plasma concentrations of unbound warfarin enantiomers, vitamin K1 and vitamin K-dependent proteins (that is, prothrombin fragments 1+2, protein C, and the protein-induced by vitamin K absence) and international normalized ratio were measured in 38 prepubertal (1 to 11 years), 15 pubertal (12 to 18 years), and 81 adult (37 to 76 years) patients given long-term warfarin therapy. Unbound oral clearance values for warfarin enantiomers and its body weight-, body surface area-, and liver weight-normalized values, as well as the pharmacodynamic parameters, were compared among the groups. RESULTS: The prepubertal, pubertal, and adult patients exhibited comparable mean plasma concentrations of unbound warfarin enantiomers for pharmacologically more active (S)-warfarin. Although the unbound oral clearance of (S)-warfarin for the prepubertal patients was significantly (P < .01) less than that for the adult group (346 versus 637 mL/min), the body weight-normalized unbound oral clearance for the prepubertal patients was significantly (P < .01) greater than that for the adults and showed a negative correlation (P < .05) with age. In contrast, no differences were observed in the liver weight-normalized unbound oral clearance for (S)-warfarin between the prepubertal and adult groups. The prepubertal patients showed significantly (P < .01 or .05) lower plasma concentrations of protein C and prothrombin fragments 1+2 and greater international normalized ratio and international normalized ratio/dose than the adults. In contrast, the pubertal patients showed largely similar pharmacokinetic and pharmacodynamic properties to adults. CONCLUSION: Liver weight may be a better parameter than body weight for estimating the warfarin doses for prepubertal patients on the basis of the corresponding adult values. Augmented responses to warfarin in children should also be taken into account for estimating warfarin doses for children.

Adolescent↗

Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients.

BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis. Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy. From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests. We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the 215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the diagnosis was definite and in 14 it was suspected. In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans. On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days. In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days. INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.

Adjuvants, Immunologic↗

A porcine homolog of the major secretory protein of human epididymis, HE1, specifically binds cholesterol.

A porcine homolog of the major secretory protein of human epididymis, HE1, was for the first time purified from the porcine cauda epididymal fluid. The HE1 homolog was secreted into the epididymal fluid as a 19-kDa glycoprotein, whose sugar moiety was gradually processed to form a 16-kDa protein during transit through the epididymis. The HE1 homolog mRNA was detected only in the caput and corpus epididymis among the porcine tissues examined. The purified HE1 homolog specifically bound cholesterol with high affinity (Kd=2. 3 microM). The binding stoichiometry was determined to be 0.94 mol/mol, suggesting that 1 mol of cholesterol binds to 1 mol of the protein. It was also found that the HE1 homolog is a major cholesterol-binding protein in the porcine epididymal fluid. The possibility that the HE1 homolog is involved in the regulation of the lipid composition of the sperm membranes during the maturation in epididymis is discussed.

Amino Acid Sequence↗

Anomalous cadherin expression in osteosarcoma. Possible relationships to metastasis and morphogenesis.

Two isoforms of the human cadherin-11/OB-cadherin gene, the intact and the variant forms, had been isolated from an osteosarcoma cDNA library. The intact form has a typical cadherin structure, whereas the variant form, generated by alternative splicing, encodes a cytoplasmic domain that is completely different from that of the intact form and lacks a homophilic cell-cell adhesion ability. At the protein level, the secreted form generated from the intact cadherin-11 is present. We examined the expression of the intact and the variant forms of cadherin-11 in 23 primary and metastatic osteosarcomas from 22 patients by reverse transcriptase-polymerase chain reaction (RT-PCR) analyses, revealing that all 23 tumors in the patients expressed the variant form and three of them expressed it prominently. On the other hand, Western blot analyses of six tumors showed that the secreted form was strongly expressed, and furthermore, expression of N-cadherin was extremely low. Overexpression of the intact cadherin-11 cDNA in osteosarcoma cell lines demonstrated that the secreted form is derived from the intact form of cadherin-11 in osteosarcoma. Immunohistochemically, cadherin-11, N-cadherin, and beta-catenin were expressed at the cell surface of fetal osteoblasts, whereas in osteosarcoma cells, they were expressed only focally or weakly in the cytoplasm. Considering the function of cadherin in carcinomas, it is suggested that the anomalous expression of human cadherin-11 in osteosarcoma and the reduced expression of N-cadherin play a role in metastasis and the irregular morphology in the highly malignant mesenchymal tumor.

Bone Development↗

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients.

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.

Antibodies, Viral↗

Dissecting aortic aneurysm in a horse.

A case of dissecting aortic aneurysm in a 4-year-old male thoroughbred horse is reported. The horse had a history of inflammation in the right thigh and a fever 2 weeks before sudden death. At necropsy, aortic aneurysms were observed from the aortic valve to the aortic arch, spreading over a distance of 40 cm. An irregular rupture of the intima of the ascending aorta was located in the cardiac side of a ramification to the tunica branchiocephalicus communis. An intramural haematoma, apparent on the cut surface and in the pericardium, had caused cardiac tamponade and sudden death.

Aortic Dissection↗

Expression of bovine cytokines in Escherichia coli.

Glutathione S-transferase fusion proteins of bovine interleukin-2 (IL-2), IL-4, IL-6 and interferon-gamma (IFN-gamma) were expressed in Escherichia coli. Complementary DNA (cDNA) for open reading frame of each cytokine without signal peptide encoding region was amplified by reverse transcriptional polymerase chain reaction method and was subcloned into pGEX-5X-1. In result, IL-6 and IFN-gamma fusion proteins in bacteria were soluble, but IL-2 and IL-4 fusion proteins were insoluble. The insoluble IL-2 fusion protein successfully refolded by urea became soluble. The recombinant IL-2, IL-6 and IFN-gamma could be obtained by the batch method using Glutathione Sepharose 4B and Factor Xa digestion, which may be useful for preparation of antisera as antigens and functional studies.

Animals↗

Expression of Recombinant bovine L-selectin in Escherichia coli and insect cells.

Bovine L-selectin was expressed in bacteria using pGEX vector and in insect cells infected with recombinant baculovirus in order to obtain recombinant protein for preparation of specific antiserum and its functional studies. In bacterial expression, L-selectin fusion protein with glutathione S-transferase was detected in the insoluble fraction with the expected molecular weight of 60 kDa by SDS-PAGE and reacted with anti-bovine CD62L monoclonal antibody in immunoblot analysis. In insect cells infected with recombinant baculovirus, a band corresponding to L-selectin was not observed in SDS-PAGE with protein staining, but they apparently reacted with anti-bovine CD62L monoclonal antibody in immunoblot analysis. Furthermore, the indirect immunofluorescence test revealed that bovine L-selectin was efficiently expressed on the surface of Sf9 cells infected with recombinant baculovirus, and flow cytometric analysis showed that the percentage of CD62L positive cells in bovine PBMC was about 66% and that most Sf9 cells infected with recombinant baculovirus had specific immunofluorescence.

Animals↗

Expression of bovine interleukin-2 in insect cells by recombinant baculovirus.

Bovine interleukin-2 (bIL-2) was expressed in insect cells infected with recombinant baculovirus. The cDNA for bIL-2 was amplified by reverse transcriptional polymerase chain reaction and recombinant baculovirus was constructed by homologous recombination. The recombinant baculovirus was plaque-purified, amplified, and then infected to Sf9 cells for expression of recombinant bIL-2 (rbIL-2). In result, the protein band corresponding to rbIL-2 could be detected on SDS-PAGE with coomassie brilliant blue staining and on immunoblot analysis reacted with mouse antiserum against bIL-2. In addition, cell proliferation assay for bIL-2 activity demonstrated that the culture supernatant of Sf9 cells infected with recombinant baculovirus enhanced the proliferation of bovine peripheral blood mononuclear cells in a dose-dependent manner.

Animals↗