Phase I study and pharmacokinetics of CPT-11 with 5-day continuous infusion.
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Adult↗
Biomedical subjects
A Kojima
Publications and source records attributed to A Kojima.
Collagen gene expression during chondrogenesis from chick periosteum-derived cells.
Chick periosteum-derived cells, which do not enter the chondrogenic cell lineage during normal bone development and growth, exhibit chondrogenic potential in high cell density culture conditions. In such cultures, collagen gene expression was temporally analyzed at the mRNA level by a reverse transcription PCR (RT-PCR) procedure, which showed that alpha 1(II) and alpha 1(IX) collagen mRNAs are coordinately increased, coincident with the onset of overt chondrogenesis, and subsequently decreased as chondrocytes exhibited hypertrophic characteristics. alpha 1(X) collagen mRNA was detected well before the onset of chondrogenesis and markedly increased along with the hypertrophic change. For alpha 2(I) collagen, both the bone/tendon form and the cartilage form of mRNA were detected throughout the culture period. This culture system provides an experimental vehicle capable of investigating the molecular events involved in the full range of chondrogenic differentiation starting from uncommitted periosteum-derived mesenchymal stem cells.
Animals↗
A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy.
Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P = 0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P = 0.0002), sex (P = 0.0009), serum albumen levels (P = 0.0018), performance status (P = 0.0026) and lactic dehydrogenase values (P = 0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months; P = 0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.
Adenocarcinoma↗
Correction of scattered photons in Tc-99m imaging by means of a photopeak dual-energy window acquisition.
We are proposing a new method for correcting of scattered photons in technetium-99m (99mTc) imaging by means of photopeak dual-energy window acquisition. This method consists of the simultaneous acquisition of two images and estimation of a scatter image included in the symmetric energy window (SW) image by the difference between these images. The scatter corrected image is obtained by subtracting the scatter image from the SW image. In order to evaluate this method, we imaged a planar and a SPECT phantom with cold lesions and calculated the contrast value with and without the scatter correction. In addition, we performed asymmetric energy window (ASW) imaging to compare with this scatter correction method for planar images. In the planar image with the tissue-equivalent material of 10 cm, the scatter correction method removed 32% of the counting rate of the SW image and improved from 0.81 to 0.94 of the contrast value for a 4 cm-diameter cold lesion, while the contrast value with the ASW was 0.87 for such a cold lesion. The scatter corrected SPECT image had a reduction of 18% of the counting rate of the SW SPECT image and improvement of approximately 11% in contrast for cold spot sizes larger than a 3 cm-diameter, compared with the SW SPECT image. In addition, a perfusion defect could be well visualized by this scatter correction method on 99mTc-HMPAO regional cerebral blood flow SPECT of a patient. Our proposed scatter correction method can improve both planar and SPECT images qualitatively and quantitatively.
Brain Concussion↗
Sub-acute toxicity of piperonyl butoxide in F344 rats.
Piperonyl butoxide, alpha-[2-(2-Butoxyethoxy)ethoxy]-4,5-methylenedioxy- 2-propyltoluene, is a pesticide synergist. F344 rats of both sex were maintained on diets containing 0, 0.6, 1.2 or 2.4% of piperonyl butoxide for 13 weeks. At the end of experimental period, they were necropsied. Selected organs were weighted and serum was analyzed by clinical chemistry. In male and female rats of the 2.4%-group, body weight gains were depressed, macroscopically, hepatomegaly was marked and liver weights were significantly higher than those of the control group. In male and female rats of all treated groups, relative kidney weights were significantly increased in a dose-dependent manner. Rats of the 2.4%-group had increased levels of albumin, cholesterol, urea nitrogen and gamma-glutamyl transpeptidase. Examination of livers of the male 2.4%-group by light microscopy showed enlarged hepatocytes with glassy cytoplasm and fatty deposition. On occasion, there was coagulative necrosis of a few hepatocytes in the periportal area and oval cell proliferation. The kidney of treated rats showed atrophy of epithelium in the proximal convoluted tubules. These results indicated that toxicity of piperonyl butoxide in rats was directed primarily to the liver and kidney.
Animals↗
Two modes of homologous C3 deposition on Ramos Burkitt's lymphoma cell substrains co-expressing DAF (CD55), CD59, and CR2 (CD21), and on cells lacking them.
We established decay-accelerating factor (DAF)/CD59-positive and -negative substrains of a human B cell line, Ramos, R(DAF+/CD59+) and R(DAF-/CD59-) respectively. Unexpectedly, treatment of R(DAF+/CD59+) cells with Mg2(+)-EGTA-serum resulted in efficient C3 deposition, while treatment of R(DAF-/CD59-) cells did not. All six substrains of R(DAF-/CD59-) cells were CR2-negative, and treatment of the cells with M177 [a membrane cofactor protein (MCP) cofactor-blocking antibody] and/or acidic buffer only minimally affected the extent of C3 deposition. However, when R(DAF-/CD59-) cells were pretreated with M177 followed by incubation with low conductivity (3 mS) Mg(2+)-EGTA-serum, C3 deposition leading to effective cytolysis was provoked. On the other hand, all seven R(DAF+/CD59+) substrains were CR2-positive and could potentially induce C3 autoactivation without cytolysis under physiological conditions. Both M177 and pH again minimally affected the extent of C3 deposition. However, conductivity altered the sensitivity to C3: at under 3.0 mS, R(DAF+/CD59+) cells became almost insensitive to alternative pathway-mediated C3 deposition. Anti-CR2 partially inhibited C3 deposition on R(DAF+/CD59+) cells and C3 deposition was abrogated on the CR2-lacking R(DAF-/CD59-) cells, suggesting that CR2 was associated with the deposition of C3. These results, together with the finding that fluid phase activation of complement did not enhance C3 deposition, suggest that there are two distinct modes of spontaneous homologous C3 deposition on human lymphoma cells. In one case, CR2 or its related molecules participates in C3 deposition overcoming the protective function of DAF/MCP and this type of C3 deposition is maximized under physiological conditions. In the other case, C3 deposition is induced by another homologous C3 activator that becomes functional under low conductivity conditions and the absence of DAF/MCP. These two modes of homologous alternative pathway activation would explain the reported instances of spontaneous C3 deposition on human B lymphoid cell lines (under physiological conditions in the presence of DAF/MCP) and on paroxysmal nocturnal hemoglobinuria erythrocytes (under low conductivity conditions in the absence of DAF/MCP).
Antigens, CD↗
An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucose-stimulated gastric inhibitory peptide secretion in rats.
Gastric inhibitory peptide release into the portal vein in response to duodenal infusion of D-glucose was studied in the presence of a leaf extract of Gymnema sylvestre, purified gymnemic acid and inhibitors of some putative glucose sensors and carriers in the intestinal lumen. Intraduodenal infusion of D-glucose significantly increased the portal immunoreactive gastric inhibitory peptide concentration in a dose-dependent manner. The increase in the portal immunoreactive gastric inhibitory peptide induced by glucose was significantly depressed by concomitantly infused leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin but not by cytochalasin B. Mannoheptulose, which inhibits glycolysis, and procaine and lidocaine, which inhibit the vagal glucoreceptor in the lumen, did not affect portal immunoreactive gastric inhibitory peptide concentrations. These results suggest that a glucose receptor, which interacts with the leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin, exists for the release of immunoreactive gastric inhibitory peptide and that the glucose receptor for gastric inhibitory peptide release is not likely to be identical with a glucose transporter or a vagal glucoreceptor in the lumen.
3-O-Methylglucose↗
Chemotherapy-induced anemia in patients with primary lung cancer.
To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).
Adult↗
Transmembrane signal transduction and osmoregulation in Escherichia coli: functional importance of the transmembrane regions of membrane-located protein kinase, EnvZ.
EnvZ is a membrane-located protein kinase which modulates expression of the ompF and ompC genes through phosphotransfer signal transduction in Escherichia coli. Previously, we developed an in vitro method for analyzing the intact form of EnvZ in isolated cytoplasmic membranes, and demonstrated that this particular form of EnvZ exhibits the ability not only of OmpR phosphorylation but also OmpR dephosphorylation. Taking advantage of this in vitro system, in this study, to assess the structural and functional importance of the membrane-spanning (transmembrane) regions of EnvZ, a set of mutant envZ genes, each of which specifies a mutant EnvZ protein with a single amino acid replacement within or very near the transmembrane regions, were isolated and characterized in terms of their in vivo osmoregulatory phenotypes and in vitro EnvZ-OmpR phosphotransfer activities. On the basis of the results, it was suggested that the transmembrane regions of EnvZ play roles in transmembrane signaling and consequent modulation of the kinase/phosphatase activity exhibited by the cytoplasmic domain in response to an osmotic stimulus.
Bacterial Outer Membrane Proteins↗
Hydroxamamide as a chelating moiety for the preparation of 99Tcm radiopharmaceuticals (I).
Hydroxamamides contain a nitrogen and an oxygen as donor atoms, and can be synthesized by the simple reaction of nitriles with hydroxylamine. Benzohydroxamamide (BHam) was investigated as a new ligand for 99Tcm. The yield of the 99Tcm-BHam complex was determined by thin-layer chromatography using cellulose strips. A high yield of the complex was obtained at room temperature over a wide pH range, even at BHam concentrations as low as 5 x 10(-7) M. Cellulose acetate electrophoresis indicated that the complex was uncharged. When the 99Tcm-BHam complex was injected into mice, it was cleared gradually from the blood by means of the hepatobiliary system with low urinary excretion. Uptake by the stomach and the spleen was low. These results demonstrate the high affinity of BHam for 99Tcm and the high stability of the 99Tcm-BHam complex. The hydroxamamide group may be a promising chelating moiety for designing new 99Tcm radiopharmaceuticals.
Animals↗
Experimental infection of cynomolgus and African green monkeys with human herpesvirus 6.
Cynomolgus and African green monkeys were inoculated with human herpesvirus 6 (HHV-6). An antibody response was first observed 10 days and 5 days after inoculation of cynomolgus monkeys and African green monkeys, respectively, and was detectable for the duration of the experiment (33 days). HHV-6 DNA was first detected by the polymerase chain reaction in mononuclear cells of one cynomolgus monkey and one African green monkey 10 days after virus inoculation, and in a total of three of four cynomolgus monkeys (75%) and four of five African green monkeys (80%) later after inoculation. Furthermore, HHV-6 DNA was detected in the lymph nodes and spleen of monkeys killed 33 days after virus inoculation. A rash was observed on the trunk of one African green monkey 13 days after virus inoculation, otherwise the infection was asymptomatic. When mononuclear cells from both groups of monkeys were cultured in medium containing concanavalin A and interleukin 2, and infected with HHV-6 in vitro, virus replication was observed. The data suggest that HHV-6 infects these species of monkey and that this system could be useful as an animal model of HHV-6 infection.
Animals↗
Establishment of transplantable tumor lines and in vitro cell lines of malignant thymoma developed in a BUF/Mna rat.
A spontaneous malignant thymoma was found in an 18-month-old female BUF/Mna rat and serially transplanted subcutaneously in both syngeneic BUF/Mna rats (designated as MTH-R) and KSN nude mice (MTH-NM) for more than 5 years. Both tumors shared the histological appearance of sarcomatoid carcinoma as seen in the original tumor. However, MTH-NM grew faster than MTH-R in the respective hosts. The MTH-NM grew in both KSN-nude mice and BUF/Mna-rnu/rnu rats but not in BUF/Mna rats, the host of the original tumor. Three continuous tissue culture cell lines (MTHC-1, MTHC-2 and MTHC-3) were established from the MTH-NM tumors at the 2nd, 15th and 17th transplantation generations, respectively. The MTH-NM tumors and latter two tissue culture cell lines carried one or more mouse chromosomes, probably acquired by cell fusion with mouse cells during passages in vivo. The presence of the mouse chromosomes was confirmed by the presence of mouse DNA and of antibodies to the MTHC-2 and MTHC-3 cells in the sera of BUF/Mna rats transplanted with MTH-NM.
Animals↗
Levels of complement regulatory proteins, CD35 (CR1), CD46 (MCP) and CD55 (DAF) in human haematological malignancies.
Levels of the membrane complement regulatory proteins, C3b/C4b receptor (CR1, CD35), membrane cofactor protein (MCP, CD46), and decay-accelerating factor (DAF, CD55), expressed on cells from patients with haematological malignancies and normal subjects were assessed by flowcytometry using the respective monoclonal antibodies (mAbs). All myeloid and most lymphoid leukaemia samples tested were CR1-negative: two of the 42 leukaemia samples expressed minute amounts of CR1. Lack of CR1 in leukaemia cells was confirmed with two mAbs raised against CR1, 31R, and 243R, which recognized different epitopes and induced different degrees of CR1-mediated fluorescent shift on flow-cytometry in granulocytes and erythrocytes. MCP was increased in most chronic myelogenous leukaemia (CML) and chronic lymphocytic leukaemia (CLL), and was also increased in majority of acute nonlymphocytic leukaemia (ANLL), acute lymphocytic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). Levels of DAF were also high in CML and CLL, and were variable in other types of leukaemia: some were DAF-negative while others expressed extremely high levels of DAF. In CML patients, the high level of MCP and the lack of CR1 were normalized after medical treatment. These results are in agreement with the data obtained with human leukaemia cell lines, and support the hypothesis that CR1 is essentially a differentiated cell antigen and that a high level of MCP reflects some malignant transformation or an immature stage in blood cells.
Antibodies, Monoclonal↗
Two species of human CRK cDNA encode proteins with distinct biological activities.
Two distinct human CRK cDNAs, designated CRK-I and CRK-II, were isolated from human embryonic lung cells by polymerase chain reaction and by screening of a human placenta cDNA library, respectively. CRK-I differed from CRK-II in that it lacked a 170-nucleotide sequence, suggesting that CRK-I and CRK-II were the products of alternative splicing. The amino acid sequences deduced from these two cDNAs differed in the carboxyl termini and contained one SH2 and either one or two SH3 domains. RNAse protection analysis demonstrated both CRK-I and CRK-II mRNAs in various human cells. Three CRK proteins, of 42, 40, and 28 kDa, were identified in human embryonic lung cells by means of antibodies against the SH2 region and the SH3 region of the bacterially expressed CRK-I protein. Transient expression of CRK-I and CRK-II cDNAs in COS7 cells showed that the former encoded the 28-kDa protein and the latter encoded the 40- and 42-kDa proteins. All human cell lines so far examined expressed the 40-kDa protein; however, expression of the 28- and the 42-kDa proteins was variable. In a comparison of the biological activity of the two human CRK proteins, both proteins were stably expressed in rat 3Y1 cells. All cell lines expressing CRK-I protein showed altered morphology, proliferated in soft agar, and grew as massive tumors in nude mice. Although CRK-II-expressing cells showed a slight morphologic change, they did not make colonies in soft agar or grow in nude mice. These results demonstrate that the two species of human CRK cDNA encode proteins which differ in their biological activities.
Amino Acid Sequence↗
Electron microscopy of renal arterial lesion in a pup infected with canine herpes virus.
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Animals↗
[Visibility of fine asbestos fibers in transmission electron microscopy analysis].
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Asbestos↗
[An autopsy case of pulmonary metastasis of cholangiocellular carcinoma associated with marked fibrotic change of the lungs].
An autopsy case of pulmonary metastasis of cholangiocellular carcinoma is presented. A 44-year-old woman was admitted to our hospital because of dyspnea, general fatigue and a sense of abdominal fullness on February 5, 1990. In November 1986, at an other hospital, she had been diagnosed as having diffuse metastatic lung tumor and multiple bone metastases, by transbronchial lung biopsy and other examinations. During the clinical course, she was not received chest irradiation and chemotherapy which induced fibrotic change of lungs. Chest X-ray film on December 21, 1986 showed diffuse nodular shadows in both lung fields. Chest X-ray film on February 4, 1990 showed diffuse reticular shadows with marked shrinkage of lung fields. She died two months after admission. The primary site of the carcinoma was not determined clinically, but was revealed by autopsy to be cholangiocellular carcinoma of the liver, with generalized metastasis. Microscopic findings of the autopsied lung showed markedly increased connective tissue around bronchi and blood vessels, in areas where microtubular adenocarcinoma was scattered. This is a very rare case of pulmonary metastasis of cholangiocellular carcinoma, associated with marked fibrotic change of the lungs during about 3.5 years. To our knowledge, this is the first reported case.
Adenoma, Bile Duct↗
Inhibitory effect by 1,25-dihydroxyvitamin D3 on concanavalin A-stimulated proliferation of rat thymic lymphocytes.
It has been reported that vitamin D3 derivatives promote the differentiation of monocytes into macrophages, while the derivatives suppress mitogen-stimulated proliferation of human peripheral blood-mononuclear cells (PBMC). However, their effect on thymic lymphocytes which are in the course of differentiation and maturation into T cells has not been thoroughly examined. The authors studied the inhibitory effect by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on concanavalin A (Con A)-stimulated proliferation of rat thymic lymphocytes and explored its mechanism. The proliferation of rat thymic lymphocytes stimulated with Con A was suppressed by 1,25-(OH)2D3 in a dose-dependent manner between a range of 10(-10) M to 10(-8) M. Because this suppressive action of 1,25-(OH)2D3 was markedly reduced by removal of coexisting adherent cells or by treatment with indomethacin which suppresses the prostaglandin E2 (PGE2) synthesis, it seems likely that PGE2, released from macrophages with the stimulation of 1,25-(OH)2D3, is involved in the suppressive action. Further studies on the inhibitory mechanism clarified that PGE2 from the contaminated macrophages suppressed the formation and release of interleukin-2 (IL-2), whereas the expression of IL-2 receptors on thymic lymphocyte with Con A stimulation was not affected. These results suggest that vitamin D3 derivatives might possibly contribute to regulation of in vitro proliferation of thymic lymphocytes.
Animals↗