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Biomedical subjects

K Kawakami

Publications and source records attributed to K Kawakami.

At least 163 records · Page 9Linked to original sources
PubMed1999

Induction of lymphocytic inflammatory changes in lung interstitium by human T lymphotropic virus type I.

Human T lymphotropic virus type I (HTLV-I) is the etiological agent of adult T cell leukemia, and reports suggest that several other clinical conditions are associated with HTLV-I infection, including myelopathy and inflammatory pulmonary diseases. However, the clinical entity of HTLV-I-associated lung disease remains unsubstantiated more than 10 years after its description. In the present study, we conducted a histopathological analysis of lung tissues of transgenic mice that expressed gene segments of HTLV-I p40(tax) regions. The aim of the study was to examine the relationship between expression of viral components and development of lung disorders. In these mice, inflammatory changes with infiltration of lymphocytes in peribronchial and perivascular areas and in alveolar septa developed at 11 wk of age and increased in incidence during the observation period (26 wk). There was a significant correlation between the pulmonary pathological changes and the level of expression of p40(tax) mRNA in the lungs. Our results provided for the first time strong evidence of a direct relationship between HTLV-I and development of bronchopulmonary infection.

Animals↗
PubMed1999

A kinetic study of protein binding to ecabet sodium using quartz-crystal microbalance.

To define the mechanism of the protection by ecabet sodium of the gastric mucosa, the characteristics of protein binding of this drug were investigated using a quartz-crystal microbalance (QCM) method. The binding rate constants (kb) and the binding amounts (delta m) were obtained from time courses of the frequency decrease (mass increase) of the QCM. The binding constants to proteins of two ecabet analogues (G1, ecabet type and G2, non-ionic ecabet type) were dependent on the pH, leading to large kb values at the acidic region. Furthermore, the kb values of G1 with the addition of bovine serum albumin (BSA) and bovine serum fibrinogen (BSF) at the acid region were larger than those of G2. The difference in kb values between G1 and G2 for porcine gastric mucin (PGM) is hardly discernible. Ecabet seems to be more heavily distributed in the ulcerous areas than in the intact mucosa, judging from the large binding constants of this drug to BSA and BSF compared with those to PGM. It is suggested that ecabet is bound to proteins by hydrophobic interaction, moreover, the electrostatic interaction between this drug and proteins (BSA and BSF) occurs at acidic pH region. On account of these interactions, ecabet sodium seems to have a more protective effect on an ulcer at intraluminal acidity than sucralfate. Finally, QCM was found to be a useful technique for detecting quantitatively the time course of binding proteins with drug.

Abietanes↗
PubMed1999

Strain differences of hypertension induced by dietary NG-nitro-L-arginine in normotensive rats.

When the potent inhibitor of nitric oxide (NO) synthesis NG-nitro-L-arginine (L-NNA) was incorporated into the diet, hypertension was induced and sustained due to the effects of the long-term inhibition of endothelium-dependent relaxing factor (EDRF)/NO. The effects of L-NNA on normotensive rats of four strains (Donryu, Sprague-Dawley (SD), Wistar, and Wistar-Kyoto (WKY)) were compared relative to control rats. L-NNA administration caused a sharp initial increase in systolic blood pressure (SBP) at 2 weeks in all animals, and this was followed by a gradual and steady increase until 4 weeks. At the end of the experiments (5 weeks), the mean SBP of Donryu and SD rats was decreased. The maximum blood pressure of Donryu and Wistar rats during the experiments exceeded 200 mmHg, but that of SD and WKY rats was below 200 mmHg. Body weight loss and death were observed only in L-NNA-fed Donryu rats. Pathological changes in the kidneys and the morbidity rates for the lesions were determined, and indicated that the Donryu L-NNA group was 100% positive. These results suggest that the Donryu strain is more sensitive to L-NNA than the other strains. That dietary L-NNA-induced hypertension in normotensive rats of the four strains provides a new artificially-induced hypertensive model in which vasoconstriction occurs mainly due to EDRF deficiency.

Animals↗
PubMed1999

Reduced immune function and malnutrition in the elderly.

An important observation in elderly subjects is their susceptibility to infection associated with a decline in host immune function. Nutrition is also an important factor that influences host defense against infection. We, therefore, evaluated the relationship between nutritional status in 155 healthy subjects ranging in age from 20 to 99 years and various immunological parameters, including the phagocytic and bactericidal activities of neutrophils and monocytes, superoxide production and chemotaxis of neutrophils, lymphocyte subsets, blastoid transformation and serum immunoglobulins. Aging was associated with increased phagocytic activity of neutrophils but not bactericidal activity, superoxide production or chemotaxis of neutrophils. Aging was also associated with a significant decrease in the number of lymphocytes as well as a decline in mature T cells and helper/inducer T cells but with increased numbers of activated T cells, suppressor T cells and natural killer cells. In addition, blastoid transformation in response to phytohemagglutinin (PHA) and concanavalin A (Con A) was significantly reduced in aged subjects. A poor nutritional status was noted in individuals 60 years of age or older. The nutritional status did not influence neutrophil function but correlated significantly with the number of lymphocytes and degree of blastoid formation with PHA and Con A stimulation. Our results suggest that the cell-mediated immunity in elderly subjects is reduced as a result of malnutrition, and that improvement of the nutritional status may enhance the immune function, likely contributing to their successful aging.

Adult↗
PubMed1999

The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts.

Chromosomal abnormalities involving the 11p15 or 11q22-23 bands have been reported in several types of human neoplasms including hematopoietic malignancies. The abnormalities are observed in therapy-related malignancies and less frequently in de novo myeloid malignancies. Abnormality of the MLL gene located on chromosome 11q23 has been well known in therapy-related myeloid malignancies, but it has been reported only recently that the inv(11)(p15q22) in de novo or therapy-related myeloid malignancies results in the fusion of NUP98 on chromosome 11p15 and DDX10 on chromosome 11q22. NUP98 is a nucleoporin that composes the nuclear pore complex and is the target gene in leukemia with the t(7;11)(p15;p15). The DDX10 gene encodes a putative adenosine triphosphate-dependent DEAD box RNA helicase. Here we present another patient with acute myelocytic leukemia (M4) transformed from chronic myelomonocytic leukemia with the inv(11) chromosome who had been treated with etoposide for a germ cell tumor. By reverse transcription polymerase chain reaction (RT-PCR) of the RNA from the leukemic cells of the patient, DDX10-NUP98 and NUP98-DDX10 fusion transcripts were detected. Our case confirms that the inv(11) is a rare chromosomal translocation that is associated with therapy-related or de novo myeloid malignancy and involves NUP98 and DDX10 but not MLL. RT-PCR of the fusion transcripts might be applied to the detection of a small number of leukemic cells in the bone marrow or blood of patients in remission or in the cells harvested for autologous transplantation.

Cell Transformation, Neoplastic↗
PubMed1999

A case of T-lineage lymphoblastic lymphoma/leukemia with t(4;11)(q21;p15) that switched to myelomonocytic leukemia at relapse.

A 51-year-old Japanese woman, initially diagnosed with T-lineage (CD2+, CD7+, CD3-, CD4-, CD8-) lymphoblastic lymphoma with t(4;11)(q21;p15), relapsed with acute myelomonocytic leukemia with the identical chromosomal abnormality. Southern-blot analysis revealed clonal rearrangements of an immunoglobulin heavy chain gene (JH) and T-cell receptor genes (J delta 1, J gamma 1, C beta 1) at first presentation, but germ line configurations of these genes at relapse. Leukemias with t(4;11)(q21;p15) may involve a hematopoietic progenitor capable of multilineage differentiation.

CD3 Complex↗
PubMed1999

Exclusion of internal iliac arterial aneurysm concomitant with abdominal aortic aneurysm repair.

BACKGROUND: To study the long-term outcomes after exclusion of internal iliac arterial aneurysm performed concomitantly with abdominal aortic aneurysm repair in patients with ruptured aortic aneurysm or other high-risk conditions. METHODS: The 31 patients who participated in this study underwent emergency (N = 9) or elective surgery (N = 22). The abdominal aortic aneurysm and the common iliac artery were excluded together with the internal iliac aneurysm in 7 patients. Forty-three (12 bilateral and 19 unilateral) internal iliac aneurysms were excluded: 35 by proximal ligation only, 5 by proximal and distal ligation, and 3 by partial resection of the proximal part of the aneurysm. The platelet count and fibrinogen level were evaluated pre- and postoperatively. Pelvic organ ischemia, classed as ischemic colitis, buttock claudication and sexual dysfunction, was examined. RESULTS: The inferior mesenteric artery was reimplanted in 21 patients. The platelet count dropped significantly postoperatively, but the fibrinogen level increased and no bleeding tendency was noted. Ischemic colitis occurred in 7 patients, resulting in colonic infarction in 2 patients. The operative mortality was 16%, and the postoperative observation periods ranged from 4 days to 217 months (mean, 60 months). The incidence of buttock claudication and sexual dysfunction was 12% and 39%, respectively. The excluded aneurysms were all thrombosed at discharge, and no late rupture was noted. The 5- and 10-year survival rate after surgery was 56% and 51%, respectively. CONCLUSIONS: Exclusion of the internal iliac aneurysm concomitant with abdominal aortic aneurysm repair shows acceptable outcome when performed in patients with high-risk conditions.

Aged↗
PubMed1999

Respiratory impedance during positive expiratory airway pressure in patients with chronic obstructive pulmonary disease.

The effect of positive airway pressure (5.0 hPa) on airway impedance (Za) and tissue impedance (Zt) during the expiratory phase in chronic obstructive pulmonary disease (COPD) patients was evaluated using random noise oscillation and a body box method. The results were then compared with those obtained from normal subjects. In normal subjects, there was no significant difference between non-expiratory positive pressure (NPEP) and positive expiratory pressure (PEP) for the Zar (real part) and Zai (imaginary part) at 10 Hz (Zar NPEP: 2.14 +/- 0.76, PEP: 1.96 +/- 0.79; Zai NPEP: 1.42 +/- 0.66, PEP: 1.40 +/- 0.70 hPa l-1 s). However, in COPD patients, Zar decreased significantly and the Zai increased significantly during PEP as compared to the values during NPEP (Zar NPEP: 7.10 +/- 1.88, PEP: 5.97 +/- 1.67, P < 0.05; Zai NPEP: -4.10 +/- 2.27, PEP: -2.99 +/- 2.62 hPa l-1 s, P < 0.05). These results suggested that both central and peripheral airway resistance decreased during PEP in COPD patients. Tissue compliance (Ct) calculated from the Zt increased significantly during PEP as compared to during NPEP, in both normal subjects and in COPD patients (normal NPEP: 0.024 +/- 0.004, PEP: 0.021 +/- 0.003, P < 0.05; COPD NPEP: 0.024 +/- 0.004, PEP: 0.014 +/- 0.004 l hPa-1, P < 0.001). This may have been indicative of the stiffened chest wall during PEP.

Adult↗
PubMed1999

[Cases of sternal metastasis except from breast cancer].

Surgical resection is the option for sternal metastasis from breast cancer. But surgical treatment is the subject of controversy for sternal metastasis except from breast cancer. Four cases of secondary malignant tumors of the sternum except from breast cancer were reported. Primary lesions included thyroid cancer, gastric cancer, malignant fibrous histiocytoma of the chest wall and multiple myeloma. In 3 cases, operation were done and they survived 11 months, 13 months and 3 years respectively. In case of secondary malignant tumor of the sternum except from breast cancer, surgical treatment should be considered.

Aged↗
PubMed1999

Partial hepatectomy strongly increased the mutagenicity of N-ethyl-N-nitrosourea in MutaMouse liver.

The relationship between cell proliferation and mutagenesis can be investigated in vivo due to the advent of transgenic animal mutation assays. In these assays, slowly proliferating tissues, such as mammary gland and liver, that are exposed to mutagens generally have longer manifestation times for mutations and lower mutant frequencies. This may be because the cells have enough time prior to cell division to repair DNA damage. We carried out this study using the MutaMouse positive selection system to investigate the effect of a high rate of cell proliferation induced by partial hepatectomy (PH) on mutation induction. We used a 2 x 2 experimental design for PH (or no PH) and 50 mg/kg N-ethyl-N-nitrosourea (ENU) (or phosphate buffer), with the chemical injected 16-19 hr after PH. In the non-ENU groups, the mean MF was slightly but not significantly higher in the PH group than in the non-PH group. In the ENU non-PH group, the MF was also slightly but not significantly increased. In the ENU PH group, in contrast, the mean MF was 7 times the mean MF of the group that received either treatment alone. These results strongly support the hypothesis that ENU induced pre-mutational DNA lesions in liver are completely repaired prior to cell division, and PH increases the mutagen-induced MF by reducing the amount of time available for such repair.

Animals↗
PubMed1999

Effects of O (6)-alkylguanine-DNA alkyltransferase deficiency in Escherichia coli as the host for the detection of mutations in lacI transgenic mice.

Transgenic mice are widely used to detect gene mutations in vivo induced by a variety of chemicals. It is known, however, that no mutagenicity of methyl methanesulfonate (MMS) is detected in epididymal sperm in various transgenic mice assays, although MMS induces the dominant lethal and specific locus mutations in male mice. To investigate the issue of whether unrepaired lesions in DNA of mature sperm can be transformed into mutations during replication of the lambda phage in Escherichia coli cells, we developed an E. coli strain YG5152, which is a derivative of strain SCS-8 but is deficient in the genes encoding O (6)-alkylguanine-DNA alkyltransferases. When lambda LIZalpha phages were treated with MMS or N-ethyl-N-nitrosourea (ENU) in vitro and infected to the E. coli strains, the mutant frequencies of lacI were markedly higher in strain YG5152 than in strain SCS-8. When Big Blue(trade mark) mice were treated with MMS (160 mg/kg) or ENU (125 or 250 mg/kg) and the phages rescued from mature sperm were infected to the strains, the mutation frequency (MF) of phages from ENU-treated mice at a dose of 250 mg/kg in strain YG5152 was about two times higher than that in strain SCS-8. However, no increase in the MF was observed in the MMS-treated mice even in strain YG5152. These results suggest that, although strain YG5152 efficiently detects ex vivo mutations caused by mutagenic alkyl adducts formed by MMS in lambda phage DNA, no detectable levels of mutagenic methyl adducts are present in mature sperm of MMS-treated mice. Possible reasons for this lack of mutagenicity of MMS in mature sperm using transgenic mice assays are discussed.

Animals↗
PubMed1999

[Factors for the onset of and the exacerbation of tuberculosis. 2. Host factors promoting the occurrence and exacerbation of tuberculosis: significance of Th1-Th2 cytokine balance].

The problem of tuberculosis is emerging again with increase in the population of aged people and immunocompromised patients in Japan. It has been well documented that cell-mediated immunity play a central role in host resistance to infection with Mycobacterium tuberculosis. A decade years ago, Mosmann et al. found that helper T (Th) cells are divided into two subsets, Th1 and Th2, based on the cytokines which they produce. Th1 cells produce IFN-gamma, while Th2 cells secrete IL-4, IL-10 and IL-13. Many recent studies have provided evidences suggesting that the Th1-Th2 cytokine balance may determine the outcome of some diseases. For example, predominant production of Th1 cytokines may prevent the occurrence of infectious diseases caused by intracellularly growing pathogens and Th2 cytokines may be involved in the exacerbation of allergic diseases. On the other hand, IL-12 plays an essential role in the differentiation of Th1 cells from naive T cells, and IL-18 potentiates this effect although it does not show such effect by itself. In the present study, we examined the role for these two cytokines in host resistance to mycobacterial infection by using an animal model with either IL-12 or IL-18 gene-disrupted mice. The organ loads of this pathogen in lung, liver and spleen were significantly larger in these gene-disrupted mice than those in control mice. There are several host factors which determines the outcome of mycobacterial infection. Among them, steroid treatment and AIDS are important factors. In this study, we determined the effect of these pathological conditions on Th1-Th2 cytokine balance and outcome of mycobacterial infection using murine models. In both conditions, the exacerbated infection was well correlated with the reduced production of IFN-gamma. Furthermore, I also discussed about the relationship between other host factors and balance in the production of Th1 and Th2 cytokines.

Animals↗
PubMed1998

Excision of the tol2 transposable element of the medaka fish, Oryzias latipes, in zebrafish, Danio rerio.

The Tol2 element is a transposable element in Oryzias latipes (the medaka fish) found in the tyrosinase gene locus of the tyrosinase-deficient mutant medaka fish and has been shown to be excised from the genome during medaka embryogenesis (Koga, A., Suzuki, M., Inagaki, H., Bessho, Y., Hori, H., 1996. Transposon element in fish. Nature 383, 30). It is, however, not known whether the Tol2 element is an autonomous element. To determine whether the cloned Tol2 element is an autonomous element and whether excision can occur also in the other fish species, the plasmid DNA harboring the Tol2 element was injected to fertilized eggs of zebrafish, Danio rerio, and the total DNA extracted from the embryos 9-10h after the injection was analyzed by PCR. When a plasmid with the full-length Tol2 element was used for the microinjection, in 39 out of 43 injected embryos, we found generation of short PCR products indicative of the loss of the Tol2 element from the injected plasmid. Ten of these cases were analyzed at the DNA sequence level, and nine of them showed either precise excision of the Tol2 element (three cases) or nearly precise excision of the element with the addition of a few nucleotides of the target duplication (six cases). When a deletion version of the Tol2 element that retained the terminal inverted repeats but lacked about one-fourth of the open reading frame-coding region was used for the microinjection, such short PCR products could not be amplified from any of the injected embryos (0 out of 30). Thus, the Tol2 element is capable of excision in zebrafish embryos, presumably dependent on a putative transposase encoded by the Tol2 element itself. This transient embryonic excision assay using zebrafish should be useful to analyze the structure and the function of the transposase and cis-elements necessary for excision. Also, this study implies the potential use of the Tol2 element in transgenesis and insertional mutagenesis in both zebrafish and the medaka fish.

Animals↗
PubMed1998

IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line (UG3) to differentiate into multinucleated giant cells in the presence of M-CSF.

The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines whose crucial roles are not fully understood. In this study, we found that interleukin (IL)-13 as well as IL-4 induced peripheral blood monocytes (PBMs) and monoblastic cell line, UG3, to differentiate into MGCs in the presence of macrophage colony-stimulating factor (M-CSF), while IL-2, IL-7 or IL-10 did not. The presence of M-CSF was essential to this MGC formation, because IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) could not replace M-CSF. IL-4 and IL-13 have been known to inhibit the formation of osteoclast-like cells in the presence of stroma cells or osteoblastic cells. But in our system without stroma cells, IL-4 or IL-13 induced some of characteristics of osteoclasts such as tartrate-resistant acid phosphatase (TRAP) activity, vitronectin receptor (vit-R) expression and resorptive activity for hydroxyapatite, but not the expression of receptors for parathyroid hormone or calcitonin. These results suggest possible involvement of IL-4 and IL-13 in MGCs and osteoclasts development, and UG3 may be useful to further investigate the roles of IL-4 and IL-13 in the formation and physiology of MGCs, and the relationship between these MGCs and osteoclasts.

Acid Phosphatase↗
PubMed1998

Computed tomography analysis of causes of local failure in radiotherapy for cervical carcinoma.

BACKGROUND: The authors analyzed the radiation dose to the periphery of the cervix and area of the cervix in relation to local failure of radiotherapy for carcinoma of the cervix using computed tomography (CT) images. METHODS: Between 1981-1990, 127 consecutive patients were treated with definitive radiotherapy. Ninety-nine of these patients had CT images taken at the time of intracavitary therapy. Of these 99 patients, 80 were eligible for this analysis. After CT scanning, isodose curves relative to the point A dose were superimposed on the CT images. The minimum percent dose and minimum dose at the periphery of the cervix were estimated. The area of the cervix also was measured. These factors were examined in relation to the local tumor control rate. RESULTS: Histograms of both the minimum percent dose and the cervical area showed significant differences between the local control and local failure groups (P <0.001). The local control rates were related to both the minimum percent dose and the cervical area, and differed significantly over and below the values of 60% and 18 cm2 (P <0.001 each), respectively. The local control patients, over and below the line: Y = -0.220X + 21.2, in which X (gray [Gy]) and Y (Gy) are the whole pelvis dose and the minimum dose, respectively, could be well differentiated with significance (91.7% vs. 25.0%; P <0.001). CONCLUSIONS: Computed tomography analysis indicated that the local tumor control rate was related strongly to the minimum percent dose, the cervical area, and the pair of whole pelvis and minimum dose values. These factors were found to be more useful than the point A dose in predicting local tumor control.

Adult↗
PubMed1998

Detection of DNA abnormalities by arbitrarily primed PCR fingerprinting: allelic losses in chromosome 10q in lung cancers.

DNA fingerprinting using arbitrarily primed PCR (AP-PCR) is useful for detecting cancer-specific DNA aberrations without targeting any particular genes or knowing any nucleotide sequences in advance. AP-PCR fingerprinting is an efficient method for finding loss of anonymous chromosomal regions in cancers. We analyzed DNA from 44 human non-small cell lung cancers by fingerprinting using a single primer and found a loss of signal intensity in a DNA fragment amplified from chromosome 10 (fragment F) in 15 tumors. The detailed location of the fragment F locus on chromosome 10q was determined by PCR-based analysis of radiation hybrid panels using a sequence-tagged site established for the fragment. In 12 of the 15 tumors, loss of the signal detected by AP-PCR fingerprinting was in agreement with the results obtained by analysis of allelic imbalances using 7 polymorphic CA-microsatellite DNA markers for loci around the fragment F locus (p=0.0009). We conclude that a hitherto unknown suppressor gene for lung cancer resides at 10q in the vicinity of fragment F.

Alleles↗
PubMed1998

Compositional Homogeneity of Liposomal Membranes Investigated by Capillary Electrophoresis.

Capillary electrophoresis has been demonstrated to be a new powerful tool for investigating the compositional homogeneity of liposomal membranes composed of phospholipids and guest molecules. In the case of charged components distributed heterogeneously on membranes, electropherograms show several distinguishable peaks even with monodisperse size distributions of liposomes because each liposomal particle carries a different amount of charge. The heterogeneity of noncharged components, when the lipids and the guest components have significantly different molar absorptivities at two different wavelengths, can also be judged from the signal ratio observed at the two wavelengths using a photodiode array detector. This new method can be used for the quality control of liposomal products. Copyright 1998 Academic Press.

Journal Article↗