[Case of immunotactoid glomerulopathy (ITG) associated with acute active glomerular lesion].
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Female↗
Biomedical subjects
T Kawamura
Publications and source records attributed to T Kawamura.
Normal immune function of monocyte-derived dendritic cells from HIV-infected individuals: implications for immunotherapy.
Dendritic cells (DC) are the most potent cells involved in the generation of primary and secondary immune responses. To assess the feasibility of using autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, as well as DC obtained from HIV-uninfected (HIV-) individuals infected in vitro with HIV. After stimulation with recombinant CD40 ligand (CD40LT), cytokine and beta-chemokine production were similar by DC from HIV- donors infected in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uninfected DC from the same donors. Production of beta-chemokines, but not of cytokines, was increased by a CXCR4-using IIIB strain-infected DC (n = 7). Stimulation of HIV-infected DC with CD40LT decreased infection in Ba-L-infected DC, but had no effect on IIIB-infected DC. Consistent with this finding, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Monocyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced similar amounts of IL-12, IL-10, and beta-chemokines, following stimulation. By contrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and increased IL-10 production. In summary, phenotype, cytokine secretion, and beta-chemokine production by DC from HIV+ individuals were normal. These cells may prove useful in boosting cellular immune responses in HIV+ individuals.
Adoptive Transfer↗
The spiroketals containing a benzyloxymethyl moiety at C8 position showed the most potent apoptosis-inducing activity.
The spiroketals containing a benzyloxymethyl moiety at the C8 position showed the most potent apoptosis-inducing activity, whereas its analogous compounds lacking any substituent at C8 or possessing ones other than the benzyloxymethyl moiety at C8 were all much less active. These results strongly suggest an important role of the benzyloxymethyl moiety linked to the C8 oxygen atom.
Apoptosis↗
Structure of mouse calpastatin isoforms: implications of species-common and species-specific alternative splicing.
Mouse calpastatin cDNAs were cloned by the method of RT-PCR using RNA isolated from myoblast C2C12 cells. Nucleotide sequencing of the isolated clones revealed an in-frame ATG codon upstream of the previously assigned translation initiation methionine. Except for the N-terminal segment, the new translatable region (domain XL) was similar to the sequence of bovine calpastatin in which domain XL was first identified. Among the isolated mouse calpastatin cDNA clones, three isoforms (mCS-a, mCS-b, and mCS-c) were identified. In domain L, mCS-b had a deletion of the region corresponding to exon 3 of the human calpastatin gene. RT-PCR analyses of various mouse tissues revealed that mCS-b was the major form and that the content of mCS-a, nondeleted form, was 5-10% in tissues including skeletal muscle, liver, brain, etc. and about 30% in the myoblast C2C12 cells. Unlike human and rat cDNAs, no other deletions were detected in mouse calpastatin domain L. Isolation of the cDNA clone of mCS-c, which lacked regions corresponding to exons 3 and 12, was obtained by chance because its expression level was under the detectable level in the mouse tissues and even in C2C12 cells.
Alternative Splicing↗
Expansion of extrathymic T cells as well as granulocytes in the liver and other organs of granulocyte-colony stimulating factor transgenic mice: why they lost the ability of hybrid resistance.
When we attempted to characterize the immunological state in G-CSF transgenic mice, a large number of not only granulocytes but also lymphoid cells expanded in various immune organs. Such lymphoid cells were present at unusual sites of these organs, e.g., the parenchymal space in the liver. We then determined the phenotype of these lymphoid cells by immunofluorescence tests. It was demonstrated that CD3intIL-2Rbeta+ cells (i.e., extrathymic T cells), including the NK1.1+ subset of CD3int cells (i.e., NKT cells), increased in the liver and all other tested organs. These T cells as well as NK cells mediated NK and NK-like cytotoxicity, especially at youth. However, they were not able to mediate such cytotoxicity in the presence of granulocytes. This result might be associated with deficiency in the hybrid resistance previously ascribed to these mice. In other words, G-CSF transgenic mice had a large number of extrathymic T cells (including NKT cells) and NK cells that mediate hybrid resistance, but their function was suppressed by activated granulocytes. Indeed, these granulocytes showed an elevated level of Ca2+ influx upon stimulation. The present results suggest that, in parallel with overactivation of granulocytes, extrathymic T cells and NK cells are concomitantly activated in number but that their function is suppressed in G-CSF transgenic mice.
Age Factors↗
Protective effect of NK1.1(+) T cells as well as NK cells against intraperitoneal tumors in mice.
Peritoneal resident cells of mice normally contain small populations of NK cells and NK1.1(+) alphabetaT cells. These populations increased after either 3LL or EL4 tumor inoculations into the peritoneal cavity. In vivo depletion of NK cell alone by anti-asialo GM1 (ASGM1) Ab significantly decreased survival time of tumor-injected mice, while depletion of both NK cells and NK1.1(+) T cells by anti-NK 1.1 Ab greatly shortened mouse survival time. NK1. 1(+) T cells in peritoneal cavity consist of a larger proportion of double-negative T cells and smaller populations of CD4(+) T cells and Vbeta8(+) T cells compared with liver NK1.1(+) T cells and normally lack Vbeta2(+) T cells. Tumor inoculation induced rapid IL-12 and IFN-gamma mRNA in tumor-infiltrating mononuclear cells (TIM). Although anti-NK1 Ab pretreatment in vivo abrogated IFN-gamma mRNA expression and IFN-gamma production of TIM, NK cell depletion alone by anti-ASGM1 Ab pretreatment retained IFN-gamma mRNA expression and partly inhibited IFN-gamma production of TIM. Peritoneal NK cells as well as NK1.1(+) T cells but not NK1.1(-) T cells of 3LL cell- or EL4 cell-injected mice showed cytotoxicities against the same tumor cells. Further, either anti-IL-12 Ab or anti-IFN-gamma Ab ip injection significantly shortened EL4 cell-inoculated mouse survival time. Our findings suggest that peritoneal macrophages activated by tumors produce IL-12 which activates NK cells and NK1.1(+) T cells to produce IFN-gamma and both NK cells and NK1.1(+) T cells are important in suppressing the growth of the intraperitoneal tumors.
Animals↗
Abundance of NKT cells in the salivary glands but absence thereof in the liver and thymus of aly/aly mice with Sjögren syndrome.
It is known that ALY/Nsc Jcl-aly/aly (aly/aly) mice that congenitally lack lymph nodes fall victim to Sjögren syndrome as a function of age. We investigated how TCRint cells of extrathymic origin and TCRhigh cells of thymic origin are distributed in various organs of these mice. Although the distribution of T-cell subsets was not different between control aly/+ and aly/aly mice in youth in any of the tested organs, the proportion of TCRint cells in the liver and spleen of aly/aly mice increased with aging. Usually, TCRint cells in the liver comprise a half-and-half mixture of a NK1. 1(+) subset (i.e., NKT cells) and a NK1.1(-) subset. In constrast, almost all expanding TCRint cells in various immune organs of aly/aly mice were found to be NK1.1(-). A large proportion of lymphocytes, including NK cells and TCRint cells, were also present in the salivary glands of aly/aly mice. Interestingly, these TCRint cells in the salivary glands contained an NK1.1(+) subset (i.e., NKT cells) that used an invariant chain of Valpha14Jalpha281 for TCRalphabeta (>50%). Moreover, gammadeltaT cells that used Vgamma 1, 2, 4/Vdelta 1, 4, 6 mRNAs, different from those of gammadeltaT cells in the liver and intestine, were abundant. Possibly reflecting the in situ generation of these T cells in the salivary glands, the expression of RAG-2 mRNA was evident by the RT-RCR method. These results suggest that (i) inflammatory lymphocytes that evoke Sjögren syndrome in aly/aly mice are NK cells or TCRint cells (both NK1.1(+) and NK1.1(-) subsets) and (ii) TCRint cells in the salivary glands might be generated in situ.
Animals↗
X-ray standing wave as a result of only the imaginary part of the atomic scattering factor.
The X-ray standing wave has been studied when the real part of the scattering factor is zero. In the symmetric Laue case, the phase of the standing wave advances by pi when the deviation parameter W changes from -1 to 1, which is the same variation as in the usual symmetric Bragg case when only the real part of the scattering factor exists. However, the phase in the former case is different from that in the latter by pi/2. By using the standing waves, the origins of the anomalous transmission and anomalous absorption effects reported by Fukamachi & Kawamura [Acta Cryst. (1993), A49, 384-388] have been analysed. The standing wave in the Laue case can give rise to a more accurate method of site determination of a specified impurity atom as well as a wider range of applications than a conventional standing-wave approach.
Journal Article↗
Keio Mutation Database for eye disease genes (KMeyeDB).
A database of mutations in human eye disease genes has been constructed. This KMeyeDB employs a database software MutationView which provides graphical data presentation and analysis as a smooth user-interface. Currently, the KMeyeDB contains mutation data of 16 different genes for 18 eye diseases. The KMeyeDB is accessible through http://mutview.dmb.med.keio.ac.jp with advanced internet browsers.
Age of Onset↗
1q23 gain is associated with progressive neuroblastoma resistant to aggressive treatment.
Neuroblastoma is one of the most common malignant tumors of childhood and is characterized by regressive and progressive disease. Genetic factors that define progression of neuroblastomas are still unknown. We performed comparative genomic hybridization (CGH) on 27 neuroblastomas and dual-color fluorescence in situ hybridization (FISH) to identify genetic aberrations associated with progressive neuroblastoma showing resistance to aggressive treatment. 17q21-q25 gains and MYCN amplification were associated with stage 4 neuroblastomas; however, these genetic aberrations had no significant relation to the progression of stage 4 neuroblastomas. A novel chromosomal gain at 1q21-q25 was found in 8 of 16 cases (50%) of stage 4 neuroblastoma. Gain of 1q21-q25 was observed in all of the progressive cases (8/8), which showed resistance to chemotherapy, including 5 fatal neuroblastomas in stage 4, whereas 1q21-q25 gain was not found in any of the 8 remission cases in stage 4. Survival analysis also showed that 1q21-q25 gain was associated with a poor outcome. High xenotransplantability in nude mice was observed for the tumors with 1q21-q25 gain (4/5; 80%). These data show that 1q21-q25 gain is strongly associated with progression of stage 4 neuroblastoma. Furthermore, by dual-color FISH analysis using cosmid clones, the 1q21-q25 gain was narrowed to increase in DNA copy number on 1q23 in the fatal type of stage 4 neuroblastoma showing this gain. These results suggest that DNA amplification at 1q23 may play a role in the development of progressive neuroblastoma in an advanced stage.
Animals↗
Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation.
The lone CX3C chemokine, fractalkine (FK), is expressed in a membrane-bound form on activated endothelial cells and mediates attachment and firm adhesion of T cells, monocytes and NK cells. We now show that FK is associated with dendritic cells (DC) in epidermis and lymphoid organs. In normal human skin, dual-color fluorescence microscopy co-localized FK expression with Langerhans cells expressing CD1a. In tonsil, FK-positive DC expressed CD83, a marker for mature DC. Human and murine cultured DC up-regulated FK mRNA expression with maturation. Furthermore, CD40 ligation, but not TNF-alpha or lipopolysaccharide treatment, of activated, migratory DC that had migrated from skin explants resulted in a 2.5-fold increase of surface expression of FK without significant alterations of expression of CD80, CD86, CD54 or MHC class II. Since FK mediates adhesion of T cells to activated endothelial cells, the increased expression of FK during DC maturation (and particularly by CD40 ligation) may play a role in the ability of T cells and mature DC to form conjugates and engage in cell-cell communication.
Animals↗
Pharmacokinetics of cisplatin in analbuminemic rats.
The effect of protein binding on the pharmacokinetics of cisplatin (cis-diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats, which genetically lack albumins, in comparison with normal rats. CDDP was reported to highly bind to serum components, and the major binder was thought to be an albumin. However, there were no significant differences in the serum disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP to analbuminemic rats as compared with normal rats. The total body clearance, Cl(tot), of platinum in normal rats was 48.7+/-22.0 mL h(-1) (5 mg kg(-1)), 55.9+/-4.04 mL h(-1) (10 mg kg(-1)) and 49.0+/-3.57 mL h(-1) (20 mg kg(-1)), whereas Cl(tot) in analbuminemic rats was 52.0+/-8.48 mL h(-1) (5 mg kg(-1)), 62.9+/-10. 8 mL h(-1) (10 mg kg(-1)) and 62.8+/-6.81 mL h(-1) (20 mg kg(-1)). The serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection were higher in both groups of rats who received CDDP than those of pre-dose level. However, there were no significant differences in the renal function tests between analbuminemic rats and normal rats. The binding of CDDP to the serum samples obtained from analbuminemic rats and normal rats was measured by a centrifuging filtration method. The binding percentages were 68.0+/-5.9% (2.0 microg mL(-1)), 56.8+/-4.1% (5.0 microg mL(-1)) and 64.6+/-4.4% (10.0 microg mL(-1)) in analbuminemic rats and 52.9+/-3.5% (2.0 microg mL(-1)), 52.2+/-3.4% (5.0 microg mL(-1)), 56.9+/-1.9% (10.0 microg mL(-1)) in normal rats. Higher binding percentages were obtained in analbuminemic rats than in normal rats. In vitro binding studies under the two incubation conditions (5 min and 2 h) showed that the binding percentages of CDDP to serum proteins were 59.2+/-3.2% (5 min) and 72.3+/-6.5% (2 h) for albumin, 42.3+/-1.9% (5 min) and 39.5+/-2.5% (2 h) for alpha(1)-acid glycoprotein (AAG) and 51.7+/-5.3% (5 min) and 49. 2+/-1.9% (2 h) for gamma-globulin. From these studies, it was elucidated that albumin is not the major ligand in the rat serum and that other proteins also have important roles in the pharmacokinetics of CDDP.
Animals↗
Overexpression of salt-tolerant glutaminase from Micrococcus luteus K-3 in Escherichia coli and its purification.
A high-expression plasmid, pKSGHE3-1, containing the salt-tolerant glutaminase (EC 3.5.1.2) from marine bacterium Micrococcus luteus K-3 was constructed. pKSGHE3-1 was made by inserting the DNA fragment (1.43 kb) containing the structural gene synthesized by polymerase chain reaction into the downstream region of the tac promoter of expression vector pKK223-3. The translational start codon was located 10 bases downstream of the Shine-Dalgarno sequence (AGGA) of pKK223-3. Escherichia coli JM109 transformed with pKSGHE3-1 exhibited more than 190-fold higher glutaminase activity than M. luteus K-3 under optimal culture conditions. The enzyme was purified to homogeneity through three column chromatography steps with a final yield of 17.1%. The recombinant enzyme showed the same enzymatic properties, including salt tolerance, as those of M. luteus K-3. This glutaminase expression system allows the production of sufficient quantities of glutaminase for basic structure-function studies including chemical modification and future X-ray crystallization analysis.
Bacterial Proteins↗
Reduced prevalence of diabetes according to 1997 American Diabetes Association criteria.
AIMS/HYPOTHESIS: We examined the prevalence of diabetes and investigated the characteristics of subjects diagnosed by the American Diabetes Association and the World Health Organization criteria. METHODS: A total of 1235 Japanese-Americans living in Hawaii and Los Angeles was studied. Of the subjects 114 were classified as previously diagnosed as having diabetes. A 75-g glucose tolerance test was given to the rest of the subjects. RESULTS: When abnormal glucose tolerance was diagnosed by the American Diabetes Association criteria, it was possible to identify only 40 % of diabetic subjects who had not been previously diagnosed compared with the current World Health Organization criteria based on a glucose tolerance test. In addition, the subjects identified by the American Diabetes Association criteria had higher glucose concentrations and had less insulin secretory capacity and they were in need of intensive treatment for diabetes. On the other hand, the subjects not diagnosed by the American Diabetes Association criteria alone were those whose glucose tolerance would be more likely to improve with lifestyle modification. CONCLUSION/INTERPRETATION: It might be better to use the fasting plasma glucose criterion advocated by the American Diabetes Association in combination with a glucose tolerance test after taking a detailed medical history. To reduce the number of subjects requiring the glucose tolerance test, priority should be given to subjects with impaired fasting glucose (6.1 </= fasting plasma glucose < 7.0 mmol/l). [Diabetologia (1999) 42: 1168-1170]
Adult↗
Serial MRI of cerebral infarcts before and after removal of an atrial myxoma.
We describe a cerebral infarct caused by atrial myxoma. A 30-year-old woman with an atrial myxoma presented with a right hemisensory deficit. MRI carried out before and after removal of the myxoma, showed multiple small bilateral white-matter infarcts which increased in number up to the surgery. A lesion in the left thalamus, which enlarged and showed contrast enhancement 4 months before surgery, resembled an old cerebral infarct by the time the myxoma was removed. The number of lesions stopped increasing after surgery. We suggest that atrial myxomas should be removed even in asymptomatic patients, to prevent cerebral infarcts due to embolism of tumour or thrombus.
Adult↗
The efficacy of CT arteriography for spinal arteriovenous fistula surgery: technical note.
We performed helical computed tomography with contrast injection into feeding arteries through a selectively introduced microcatheter to provide precise definition of the vascular and bony structure of the spine in patients with spinal arteriovenous fistula. This selective CT arteriography reliably showed structures including abnormal epi- and intradural feeding arteries, the fistula, perimedullary draining veins and surrounding vertebrae preoperatively with a minimal contrast medium load. This technique can facilitate safe, minimally invasive surgical obliteration of the fistula and a favorable outcome.
Angiography↗
Association of beta3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men.
The Trp64Arg variant of the beta3-adrenergic receptor (beta3-AR) gene is relatively common in Japanese people. We hypothesized that this variant may be associated with obesity and insulin resistance when combined with a westernized lifestyle. To test this hypothesis, we investigated the relationships between the beta3-AR gene variant and obesity and insulin resistance in Japanese-American men, who are known to have a higher prevalence of type 2 diabetes mellitus (DM). The subjects were 152 Japanese-American men living in Hawaii, 83 with normal glucose tolerance (NGT), 40 with impaired glucose tolerance (IGT), and 29 with DM. The frequency of the Trp64Arg allele of the beta3-AR gene was 0.18, almost identical to that of the mainland Japanese. The prevalence of the Trp64Arg allele was 30.1% in NGT, 35.0% in IGT, and 41.4% in DM subjects (nonsignificant). The Trp64Arg variant of the beta3-AR gene showed no significant relationship with obesity or insulin resistance in NGT subjects. However, fasting and 2-hour insulin levels and insulin resistance as determined by homeostasis model assessment (HOMA) were significantly higher in IGT subjects with the Trp64Arg variant. Although indices of obesity were the same in IGT subjects with and without the Trp64Arg variant, differences in the body mass index (BMI) and percent body fat between NGT and IGT subjects were greater for individuals with the Trp64Arg variant. Thus, there is an association between the Trp64Arg variant of the beta3-AR gene and insulin resistance in Japanese-Americans with IGT.
Adult↗
Risk modification in lung cancer by a dietary intake of preserved foods and soyfoods: findings from a case-control study in Okinawa, Japan.
To disclose the association of dietary intake of preserved foods and soyfoods with lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan, from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (1) The more the miso soup intake, the higher the risk (test for trend: P = 0.001 for males; P = 0.043 for females). (2) Frequent intake of pickles (excluding salted fish) tended to be linked with an elevated risk in males. The adjusted odds ratio (OR) for once or twice per week or more, relative to less than once a month was 1.88 (95% confidence interval (CI): 1.26-2.81). (3) Frequent intake of soybeans was associated with a decreased risk in men (OR: 0.63, 95% CI: 0.40-0.98 for once or twice per week or more, relative to less than once a month). (4) Daily consumers of tofu were at a decreased risk, particularly for squamous cell carcinoma; the OR (95% CI) being 0.55 (0.34-0.89) in males and 0.14 (0.02-0.89) in females. These findings suggested deleterious effects of preserved foods and protective ones of soyfoods rich in isoflavones.
Adenocarcinoma↗