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Biomedical subjects

A Kojima

Publications and source records attributed to A Kojima.

At least 181 records · Page 10Linked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

[A case of myocardial infarction with normal coronary arteriogram in combined valvular disease].

In this report, we presented a case of myocardial infarction with angiographically normal coronary artery, possibly caused by coronary thromboembolism due to combined mitral and aortic valvular lesions. Embolism arising from the mitral valve or left atrium might preferentially enter the coronary arteries because of the turbulence produced by the associated aortic valve lesion. Her impaired cardiac function, due to valvular lesions and myocardial infarction, has improved after double valve replacement.

Adult↗
PubMed1992

Feasibility study on quality-of-life questionnaires for patients with advanced lung cancer.

In order to evaluate quality-of-life (QOL) questionnaires, we studied the reliability and validity of the self-rating forms: A, comprising 16 questions; B, comprising 39 questions (Table II and III), in a special study supported by the Ministry of Health and Welfare. Sixty-four patients with inoperable lung cancer and 50 patients with chronic, non-malignant disease were entered into the study. Form A was translated and modified to Japanese culture from Schipper's Functional Living Index-Cancer, and Form B was of our own design. The internal consistency of the forms was examined by Cronbach's alpha coefficient. Both forms except for aspects of physical and social concern on form B, had alpha values greater than 0.65. A concurrent validity with performance status was shown over all aspects of concern (Pearson's correlation, r greater than 0.27, P less than 0.05) except for social (forms A and B) and psychological (form B). Analysis of variance of the QOL scores revealed significantly lower scores for the cancer patients than for the non-malignant-disease patients, except for the social aspect of concern (P less than 0.001). Factor analysis, using the principal component method, identified four major factors to account for 60 and 42% of the total variance on forms A and B, respectively. The factors were: patient's mood, anxiety over disease and treatment, relationships with other people, physical capability. In conclusion, this has been the first feasible study to show that QOL forms from the West could be used in Japan with some modifications. We are at present studying successive changes in QOL for advanced lung cancer patients in clinical trials.

Adult↗
PubMed1992

[A successful surgical case of acute myocardial infarction in total obstruction of the left main coronary arterial ostium].

Cardiogenic shock due to acute myocardial infarction in an 81-year-old man with total obstruction of the left main coronary arterial ostium was successfully treated with coronary artery bypass grafting. Although this procedure was successful there are some problems in the surgical management of this condition with regard to myocardial protection and preoperative evaluation of poorly visualized left coronary system. It is necessary to infuse first a large volume of high pressure cardioplegic solution and then follow it with another infusion of the solution, through the vein graft, at the regular volume and pressure. Furthermore, the complete revascularization of the left coronary system by vein grafts is recommended.

Aged↗
PubMed1992

Acquired factor VIII inhibitor in a patient with adenocarcinoma of the lung.

A 58-year-old man developed an acquired factor VIII inhibitor in association with adenocarcinoma of the lung. Laboratory examinations showed a marked prolonged activated partial thromboplastin time and a low level of factor VIII activity. Further study revealed his serum to have a factor VIII inhibitor which was characterized as an IgG. Treatment with prednisolone was successful in reducing the inhibitor so that the bleeding manifested by epistaxis and subcutaneous hemorrhages in the extremities ceased. Circulating inhibitors against factor VIII associated with malignancies appear to be very rare. Fourteen patients with factor VIII inhibitors associated with malignancies were reviewed.

Adenocarcinoma↗
PubMed1992

[Analysis of blood coagulation and fibrinolysis in rheumatoid arthritis using the urokinase activated thromboelastography].

The urokinase activated thromboelastography is useful for the analysis of blood coagulation and fibrinolysis in rheumatoid arthritis (RA). In 43 RA patients without extraarticular symptoms (mean year old +/- SD = 50.3 +/- 10.9) and 20 healthy control subjects (mean year old +/- SD = 49.5 +/- 13.8, which is not significant), we have examined reaction time (r), coagulation time (k), r+k, maximal amplitude (ma), lysis time (LT) of the urokinase (final density = 85U/ml) activated platelet rich plasma thromboelastography. In RA patients r, k, r+k are shorter, ma is larger, LT is longer than in control subjects. Especially, k, ma and LT are remarkably statistically significant. these findings suggest that most of RA patients have hypercoagulability and/or prolongation of lysis time simultaneously, k, ma and LT are pathophysiologically important.

Adult↗
PubMed1992

Decreased perfusion in myocardial region of normal donor artery secondary to collateral development. Stress 201Tl myocardial emission CT performed in patients with single vessel exertional angina having collaterals.

Thirty-one patients suffering from single vessel exertional angina with collaterals (Group A) were evaluated by stress 201T1 myocardial emission CT (Tl-SPECT) with 16 controls of severely stenotic single vessel exertional angina without collaterals (Group B). Group A included 21 patients (68%) who showed an extensive perfusion defect in double artery myocardial regions, including the normal donor artery myocardial region (DMR). However, there were no such cases in Group B, giving a significant difference between these 2 groups (p less than 0.001). Four patients in Group A, having a perfusion defect both in DMR and in the collateral dependent myocardial region (CMR) underwent a successful percutaneous transluminal coronary angioplasty (PTCA) with disappearance of collaterals. Tl-SPECT findings after PTCA showed no perfusion defect either in CMR or in DMR. This has been explained on the basis that the coronary collaterals stole blood and produced perfusion defect in DMR.

Aged↗
PubMed1991

[Clinical evaluation of per-rectal scintigraphy using I-123 IMP--evaluation of the portal hemodynamic changes after TAE].

Per-rectal portal scintigraphy using I-123 IMP was performed before and after TAE in 29 patients with hepatoma. Index of porto-systemic shunt (PSS index) was obtained by lung/(lung + liver) uptake ratio at 30 min after administration of IMP. The influence of TAE on portal circulation was evaluated by using this PSS index. PSS index increased 16 of 29 patients (55.2%) after TAE. PSS index increased after TAE especially in cases of severe liver dysfunction before TAE, marked portal involvement, and embolization of a larger liver volume. PSS index also increased when there was deterioration of esophageal varices, ascites, and hepatic coma after TAE. PSS index is useful for evaluation of portal circulation after TAE.

Amphetamines↗
PubMed1991

Transmembrane signal transduction and osmoregulation in Escherichia coli. Functional importance of the periplasmic domain of the membrane-located protein kinase, EnvZ.

The EnvZ protein is presumably a membrane-located osmotic sensor which is involved in expression of the ompF and ompC genes in Escherichia coli. Previously, we developed an in vitro method for analyzing the intact form of the EnvZ protein located in isolated cytoplasmic membranes, and demonstrated that this particular form of the EnvZ protein exhibits the ability not only as to OmpR phosphorylation but also OmpR dephosphorylation. In this study, to gain an insight into the structural and functional importance of the putative periplasmic domain of the EnvZ protein, a set of mutant EnvZ proteins, which lack various portions of the periplasmic domain, were characterized in terms of not only their in vivo osmoregulatory phenotypes but also in vitro EnvZ-OmpR phosphotransfer reactions. It was revealed that these deletion mutant EnvZ proteins are normally incorporated into the cytoplasmic membrane. Cells harboring these mutant EnvZ proteins showed a pleiotropic phenotype, namely, OmpF- Mal- LamB- PhoA-, and produced the OmpC protein constitutively irrespective of the medium osmolarity. It was also suggested that all of these mutant EnvZ proteins were defective in their in vitro OmpR dephosphorylation ability, while their OmpR phosphorylation ability remained unaffected. These results imply the functional importance of the periplasmic domain of the EnvZ protein for modulation of the kinase/phosphatase activity exhibited by the cytoplasmic domain in response to an environmental osmotic stimulus.

Bacterial Outer Membrane Proteins↗
PubMed1991

Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion.

A phase I study of cis-diammine(glycolato)platinum (254-S; NSC 375101D) was conducted in 15 patients with refractory or relapsing malignancy by 5-day continuous i.v. infusion. Three to 5 patients per dose were given 50, 75, 87.5, or 100 mg/m2/120 h (10-20 mg/m2 daily for 5 days). Toxicity evaluation and pharmacokinetic analysis were performed in 15 and 14 patients, respectively. Thrombocytopenia and neutropenia were the dose-limiting toxicities at the maximum tolerated dose of 87.5 mg/m2/120 h (17.5 mg/m2/day); however, nonhematological toxicities including renal toxicity, nausea and vomiting, and peripheral neuropathy were mild and well tolerated. The nadir of platelets and neutrophils was observed 4 and 5 weeks, respectively, after the initiation of drug infusion. Plasma and urine samples were obtained during and after infusion for quantification by atomic absorption spectrophotometry of total and free platinum levels derived from 254-S. The maximum level of total platinum was obtained after 120 h of infusion, whereas the steady state concentration of free platinum in the patients given 75 mg/m2 or more was over 0.1 microgram/ml. Free platinum levels declined monophasically, with half-lives of 0.65-2.56 h/100 mg/m2 dose. The mean area under the concentration versus time curve (AUC) in the patients treated with 75 mg/m2 was 1069 micrograms/ml, which was similar to that obtained in the patients receiving 100 mg/m2 of 254-S by i.v. drip infusion over 30 min. There was a direct correlation between the dose administered and the AUC of platinum (R = 0.757, P = 0.002) or the steady state plasma concentration of free platinum (R = 0.763, P = 0.002). The percentage of platinum excreted in urine 144 h after the initiation of infusion ranged from 73.1 to 100% for each dose level. No significant relationship was established between creatinine clearance in patients before treatment and the AUC or steady state concentration of free platinum. The plasma platinum AUC showed a linear correlation with the percentage of change in leukocytes [formula: see text] (R = 0.736, P = 0.003). In conclusion, the recommended phase II dose for a continuous infusion of 254-S is 75.5 mg/m2/120 h every 6 hours.

Adult↗