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Biomedical subjects

H Kagawa

Publications and source records attributed to H Kagawa.

At least 37 records · Page 2Linked to original sources

Platelet activation markers and soluble adhesion molecules in patients with systemic lupus erythematosus.

We assessed the role of platelet activation markers (PMPs, Annexin V and CD62P on activated platelets), cytokines (IL-1 beta, IL-4, IL-6, IFN- gamma, GM-CSF, and TNF alpha ), and soluble factors (sIL-2R, TM, sHLA-1, beta(2) -m, sVCAM-1, sPECAM-1, sP-selectin and sE-selectin) in vascular damage related to SLE. There were differences in the levels of PMPs and platelet activation markers between the SLE patients and controls (PMPs: 493+/-82 vs. 328+/-36, p<0.05; plt-CD62P; 8.5%+/-1.2 % vs. 4.6%+/-0.7 %, p<0.05; plt-Annexin V: 11.3%+/-2.1 % vs. 4.9%+/-0.6 %, p<0.01). There were no differences in the levels of IFN- gamma between the groups. However, the levels of IL-1 beta, IL-4, IL-6, GM-CSF, TNF alpha, and soluble factors were higher in the SLE patients than in the controls. The levels of IL-4, IL-6, beta2 -m, sIL-2R, sVCAM-1, sP-selectin, and sE-selectin in SLE patients with elevated sTM levels were higher than those in the SLE patients without elevated sTM levels. On the other hand, elevations of sIL-2R, sVCAM-1, and sP-selectin were not found in patients with Behçet disease or rheumatoid arthritis. The levels of platelet CD62P, platelet annexin V, and PMP were significantly elevated in high-sTM patients. These findings suggest the possibility that activated platelets and cytokines participate in the pathogenesis of SLE in patients with elevated sTM levels.

Adult↗

[Systemic inflammatory response syndrome triggered by necrotizing cholecystitis after treatment of underlying low titer cold agglutinin disease].

In April 1996, a 77-year-old man initially presented with fever, rash and polyarthralgia, and was diagnosed as having low titer cold agglutinin disease with acute hemolytic anemia. The patient's condition and laboratory findings improved after administration of corticosteroid (prednisolone 60 mg). In June 1996, however, he developed acute cholecystitis and died due to sepsis, disseminated intravascular coagulation and multiple organ failure. During the course, the levels of inflammatory cytokines such as TNF-alpha and IL-6 were correlated with the pathology, and the disease was diagnosed as systemic inflammatory response syndrome (SIRS). Autopsy revealed necrotizing cholecystitis, erythrophagocytosis in the liver, and cytomegalovirus infection in the lung and gall bladder. This was considered to be a rare case of low titer cold agglutinin disease complicated by SIRS.

Aged↗

Serum levels of soluble CD30 in autologous peripheral blood stem cell transplantation.

High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important method of treatment for hematological and solid tumors. We examined levels of interleukin(IL)-4, interferon (IFN)gamma, soluble (s) CD30, and sIL-2 receptor (R) before and after autologous PBSCT, and compared findings for PBSCT with those for bone marrow transplantation (BMT). We found significantly higher IL-4 levels 1 and 3 weeks after PBSCT than before PBSCT, while IFNgamma levels remained almost unchanged after PBSCT. IFNgamma levels were increased 3 weeks after BMT, although no increase in IL-4 level was observed. The serum sCD30 level was significantly higher 3 weeks after PBSCT, but not following BMT. For 34 samples on days 0 and 21 from 17 patients undergoing PBSCT, a strong correlation was observed between sCD30 and sIL-2R levels (r = 0.43, P < 0.01). However, no significant correlation between sCD30 and sIL-2R levels was found for BMT patients. These findings suggest that sCD30 is a useful marker for evaluating immunological activity following autologous PBSCT, and that the immunological conditions after autologous PBSCT may be associated with helper-T-cell-2-type immune responses.

Adult↗

Prenatal detection of a high-risk group for intrauterine growth restriction based on sonographic fetal biometry.

OBJECTIVE: This study was performed to evaluate the significance of sonographic fetal biometry in predicting low birth weight. METHOD: Five hundred and sixty-eight single-term pregnancies were analyzed. They were stratified into seven subgroups by birth weight deviation (BWD). Among the 568 pregnancies, 115 were revealed to be small-for-gestational-age (SGA) (birth weight less than mean -1.5 S. D.). When IUGR was suspected by routine sonographic fetal biometry, 'IUGR work-up' was carried out. The diagnostic performance of our screening method for the detection of SGA pregnancies in the general population was calculated. RESULT: The sensitivity, specificity, positive predictive value, negative predictive value and odds ratio of our screening method for the detection of SGA pregnancies in the general population were 73.0, 96.6, 83.2, 98.0% and 131.0, respectively. CONCLUSION: These data suggest that sonographic biometry is useful for the prenatal detection of high-risk cases of fetal growth restriction.

Biometry↗

Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpura.

We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-gamma, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19- cells) or cytotoxic T cell frequency (CD8+ CD11b- cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8- cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r = 0.687, p < 0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and -negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway.

Adult↗

Whole blood prothrombin time using diluted tissue factor is shortened in spontaneous hypertensive rats.

Clinical screening tests for blood coagulation that use plasma as samples cannot estimate the participation of platelets, leukocytes, and erythrocytes in blood coagulation system. We developed an assay to evaluate the total coagulation ability of blood and whole blood prothrombin time (WPT) using the principle of prothrombin time with the diluted-tissue factor as a trigger and a newly developed apparatus, STA, viscosity change detection system (electromagnetic clot detection). The activation of platelets by Ca ionophore shortened WPT and increased the expression of CD62P on the platelet surface. WPTs in citrated blood of spontaneous hypertensive rats (SHR) were significantly shorter than those of controls, Wistar Kyoto rats (WKY). Plasma levels of thrombin-antithrombin III (TAT) in SHR were significantly higher than those of WKY. Moreover, WPT and TAT levels were significantly correlated. Based on these results, WPT was found to be useful to estimate the activation of blood coagulation in whole blood.

Animals↗

Unique expression of gonadotropin-I and -II subunit genes in male and female red seabream (Pagrus major) during sexual maturation.

Two distinct gonadotropins (GTHs) have been demonstrated in a number of teleost fishes. Although the physiological roles of GTHs have been extensively studied in salmonids, little is known about their biological functions in nonsalmonid fishes. In this study, to elucidate the role of GTH-I and GTH-II in reproduction, we cloned the alpha-glycoprotein subunit (alphaGSU) and gonadotropin beta subunits (Ibeta and IIbeta) of red seabream using the 5'- and 3'-RACE methods and used these cDNA probes to reveal changes in mRNA levels of each subunit during sexual maturation of both male and female red seabream. The nucleotide sequences of alphaGSU, Ibeta, and IIbeta are 629, 531, and 557 base pairs long, encoding peptides of 117, 120, and 146 amino acids, respectively. The deduced amino acid sequence of each mature subunit showed high homology with those of other teleosts. Northern blot analysis showed that Ibeta mRNA levels of males increase in association with gonadal development, whereas those of females remain low throughout sexual maturation, indicating sexual dimorphism in the expression pattern of Ibeta. In contrast, IIbeta mRNA levels of both sexes are maintained at high levels from the beginning of gametogenesis to spawning season. These results are different than those of salmonids and suggest that GTH-I may have important roles in male, but not female, gametogenesis. GTH-II may be involved in regulation of early and late gametogenesis in both male and female red seabream.

Amino Acid Sequence↗

Vitamin-D receptor genotype and renal disorder in Japanese patients with systemic lupus erythematosus.

BACKGROUND/AIMS: It is known that allelic variants of the gene encoding the vitamin-D receptor (VDR) detected by BsmI increase the risk of some advanced malignant tumors, suggesting that such variants may cause functional differences in 1,25(OH)(2) vitamin D(3). We examined the VDR genes of Japanese systemic lupus erythematosus (SLE) patients, to determine whether different genotypes are correlated with SLE or its criteria. METHODS: VDR genotyping of 58 unrelated Japanese SLE patients was performed based on polymerase chain reaction-restriction fragment length polymorphism (RFLP). Following amplification, products were digested with BsmI. The RFLPs were coded as Bb, where the uppercase letter signifies the absence of the digested site and the lowercase letter signifies the presence of the site. RESULTS: The frequency of the VDR BB genotype was significantly higher in SLE patients (15.5%, n = 9/58, p < 0.0001) than in controls (5.7%, n = 5/87). Furthermore, a larger proportion of bb individuals was observed among patients with nephrotic syndrome (61.5%, n = 8/13) than among SLE patients without renal dysfunction (35.7%, n = 10/28). There was a significant tendency for the population of patients with the bb genotype to be correlated with that of patients with renal dysfunction (p = 0.0304). CONCLUSION: These findings suggest that the BB genotype might trigger the development of SLE, and that the bb genotype is associated with lupus nephritis.

Adult↗

Calsequestrin, a calcium sequestering protein localized at the sarcoplasmic reticulum, is not essential for body-wall muscle function in Caenorhabditis elegans.

Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR). Here we describe the identification and functional characterization of a C. elegans calsequestrin gene (csq-1). CSQ-1 shows moderate similarity (50% similarity, 30% identity) to rabbit skeletal calsequestrin. Unlike mammals, which have two different genes encoding cardiac and fast-twitch skeletal muscle isoforms, csq-1 is the only calsequestrin gene in the C. elegans genome. We show that csq-1 is highly expressed in the body-wall muscles, beginning in mid-embryogenesis and maintained through the adult stage. In body-wall muscle cells, CSQ-1 is localized to sarcoplasmic membranes surrounding sarcomeric structures, in the regions where ryanodine receptors (UNC-68) are located. Mutation in UNC-68 affects CSQ-1 localization, suggesting that the two possibly interact in vivo. Genetic analyses of chromosomal deficiency mutants deleting csq-1 show that CSQ-1 is not essential for initiation of embryonic muscle formation and contraction. Furthermore, double-stranded RNA injection resulted in animals completely lacking CSQ-1 in body-wall muscles with no observable defects in locomotion. These findings suggest that although CSQ-1 is one of the major calcium-binding proteins in the body-wall muscles of C. elegans, it is not essential for body-wall muscle formation and contraction.

Amino Acid Sequence↗

[New theory predicting molecular shapes (deviation of framework and orbital from those of norm)].

The aim of this paper is to understand why the molecule has its own structure (optimized geometry) which differs from the standard one (norm). Basic strategy to obtain the optimized geometry is to start from the norm. The emphases are 1) a theory predicting polarization exemplified by norbornene HOMO distortion and 2) when we apply any theory of 1), what framework should we use? The latter is very important due to the fact that the optimized geometries of cations and anions differ greatly from the norms. For polarization, we have elaborated "in-bond orbital method." The method is based on the well-known correlation between separated atoms and united atom and able to represent polarization within minimum basis set only by the first-order perturbation theory. For cationic and anionic hydrocarbons, a new method consisting of an assumption and a few recipes is developed. Although the assumption that the framework distortion surpasses the orbital distortion (polarization) is based solely on organic chemist's intuition, this method correctly suggests the structure (framework) to which the in-bond orbital method should be applied. All of the optimized geometries used in this study are obtained by HF/6-31 + G*.

Anions↗

Compensatory renal hypertrophy and changes of renal function following nephrectomy.

We studied the changes in the serum creatinine level and the volume of the remaining kidney following nephrectomy using contrast-enhanced compounded tomogram (CT) scans. Twenty-five patients undergoing nephrectomy for renal cell carcinoma without obvious disease in the remaining kidney were carefully followed for a period of at least two years at our hospital. Twelve patients received follow-up CT scans each year after nephrectomy. The ellipsoid volume of the kidney was calculated by measuring the 3-dimensional size on CT scans. The mean relative volume (%) of the remaining kidney increased up to year 3 postoperatively, and the final mean relative volume at varying periods from years 2 to 7 was 120%. Kidneys that were smaller prior to nephrectomy showed a tendency to have a larger final relative volume after nephrectomy, although there was no significant correlation between the kidney volume prior to nephrectomy and at final measurement. The mean serum creatinine level was significantly increased at one year after nephrectomy, but it decreased significantly over time. Therefore, both compensatory renal hypertrophy and improved renal function seemed to be established within several years after nephrectomy. However, the improvement of serum creatinine was delayed compared with the increase of kidney volume. That is, renal plasma flow might be increased early by compensatory renal hypertrophy, followed within a few years by an increase in glomerular filtration and a decrease of serum creatinine.

Adult↗

Retroperitoneoscopic heminephrectomy of the right upper collecting system emptying into an ectopic ureterocele in a 5-year-old girl: a case report.

A 5-year-old girl with a history of recurrent urinary tract infection since the age of 14 months was diagnosed as having a right duplicated urinary collecting system with the upper ureter ectopically opening in the urethra. She underwent retroperitoneoscopic heminephrectomy for a right dysplastic kidney and open ureterocelectomy and reimplantation of the refluxing lower ureter via Pfannenstiel incision. She survived the procedure without serious complications and resumed normal daily activities by day 6. To the best of our knowledge, this case is the 16th case of laparoscopic heminephrectomy for pediatric patients and the first case treated by the retroperitoneal approach in the English literature.

Child, Preschool↗

[A patient with hemorrhage originating from an unknown coagulation pathway inhibitor].

The hemorrhagic disorders associated with circulating anticoagulant are rare but well known as the disease derived from inhibitors(alloantibody or autoantibody), which arise against specific coagulation factors. We encountered a patient with hemorrhage at the lower limbs originating from an unknown coagulation pathway inhibitor. Activated partial thromboplastin time(APTT) prolonged and cross mixing test indicated a coagulation pathway inhibitor. Levels of coagulation factors VIII, IX, XI, and XII were extremely low. Predonine therapy was effective to stop the hemorrhage. To clarify the inhibitor, we treated the patient's plasma with protein A Sepharose, and the factor VIII activity was recovered to a normal level after passing through the column. Gel filtration of the patient's plasma and protein A Sepharose adsorbed fraction of the patient's plasma with Superdex 200 revealed that the inhibitor activity against blood coagulation eluted at the position of IgG, which was detected by the prolongation of APTT of normal pooled plasma. These data indicated that the inhibitor was IgG and its inhibitory spectrum was non-specific and broad. The results of laboratory tests and the clinical features in our patient were similar to those in a previous study by Dahlback(Blood 62, 218-225, 1983). The hemorrhagic abnormality of that patient was derived from the autoantibody to phospholipid, which inhibits the activation of prothrombin. An investigation into the effect of anti-phospholipid antibody in our patient is currently being performed in our laboratory.

Adult↗

Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies.

We investigated the significance of platelet activation and platelet-derived microparticles (PMP) in 14 patients with systemic inflammatory response syndrome (SIRS) and hematological malignancies. In the phenotypic analysis of lymphocytes, there was a significant decrease of total and activated T cells after panipenem/betamipron (PAPM/BP) treatment (p<0.05). The percentages of helper/inducer T cells and suppressor/cytotoxic T cells were insignificantly decreased after PAPM/BP treatment. The number of natural killer (NK) cells of potent activity was significantly decreased after treatment (p<0.05). The levels of the cytokines interleukin (IL)-1beta, IL-6, and IL-8 in the patients were increased before treatment. IL-1beta concentrations were not changed after treatment. In contrast, the IL-6 and IL-8 levels were significantly decreased (p<0.05) after treatment, while tumor necrosis factor (TNF)-alpha and interferon gamma remained almost normal. We found an increase of soluble IL-2 receptor (sIL-2R) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in the patients before treatment. After treatment, the sIL-2R concentrations tended to be decreased and sVCAM-1 levels showed a significant decrease (p<0.01). In contrast, soluble thrombomodulin (sTM) level did not change. Regarding the platelet activation markers, CD62P, CD63, and PMP levels in the patients were increased before treatment. CD62P and CD63 tended to be decreased after treatment, whereas PMP levels were significantly reduced from 1,056+/-103 to 762+/-64/10(4) platelets (p<0.05). Furthermore, CD62P, CD63, and PMP correlated with the levels of IL-6 and IL-8. These results suggest that activated platelets and PMP may be predictive markers in pre-disseminated intravascular coagulation and hypercytokine conditions related to SIRS.

Adult↗

Genomic organization, expression, and analysis of the troponin C gene pat-10 of Caenorhabditis elegans.

We have cloned and characterized the troponin C gene, pat-10 of the nematode Caenorhabditis elegans. At the amino acid level nematode troponin C is most similar to troponin C of Drosophila (45% identity) and cardiac troponin C of vertebrates. Expression studies demonstrate that this troponin is expressed in body wall muscle throughout the life of the animal. Later, vulval muscles and anal muscles also express this troponin C isoform. The structural gene for this troponin is pat-10 and mutations in this gene lead to animals that arrest as twofold paralyzed embryos late in development. We have sequenced two of the mutations in pat-10 and both had identical two mutations in the gene; one changes D64 to N and the other changes W153 to a termination site. The missense alteration affects a calcium-binding site and eliminates calcium binding, whereas the second mutation eliminates binding to troponin I. These combined biochemical and in vivo studies of mutant animals demonstrate that this troponin is essential for proper muscle function during development.

Amino Acid Sequence↗

Regulation of gap junctions and oocyte maturational competence by gonadotropin and insulin-like growth factor-I in ovarian follicles of red seabream.

The in vitro effects of human chorionic gonadotropin (hCG) and human insulin-like growth factor-I (IGF-I) on the formation of oocyte-granulosa cell (heterologous) and granulosa cell-granulosa cell (homologous) gap junctions (GJ) were determined during the course of development of oocyte maturational competence (OMC) in ovarian follicles of red seabream. Incompetent, full-grown follicles were incubated in hCG (10 IU/ml), IGF-I (10 nM), or hormone-free medium for 0, 6, and 12 h and examined by electron microscopy. Qualitative analysis indicated that homologous and heterologous GJ were relatively rare in incompetent follicles and remained rare if they were maintained in control medium. However, both types of GJ were readily observed in follicles treated with hCG or IGF-I. For quantitative analysis, we measured changes in the combined numbers of both GJ types, since discrimination between the two was not always possible. The numbers of GJ along 125 micrometer of granulosa cell-zona radiata border were counted in three follicles/treatment. GJ markedly increased with time in the presence of hCG or IGF-I but not in control medium (Duncan's multiple range test; P < 0.05). Functional assays confirmed that the hormonal treatments also induced OMC. Naturally competent follicles sampled at the appropriate stage of the reproductive cycle contained high levels of both types of GJ suggesting that the OMC-associated increase in GJ is physiologically relevant. In view of similar, earlier results with the Atlantic croaker, the present results support the concept that an increase in homologous and heterologous GJ is a general developmental event associated with the acquisition of OMC in teleost ovarian follicles. Also, a novel finding of this study is that IGF-I can regulate heterologous and homologous GJ in intact ovarian follicles.

Animals↗

Lytic activity and biochemical properties of lysozyme in the coelomic fluid of the sea urchin strongylocentrotus intermedius

Lysozyme was identified in the coelomic fluid including coelomocytes of the sea urchin Strongylocentrotus intermedius, and its lytic activity and biochemical properties were examined in this study. The urchin lysozyme was electrophoretically fractionated to a single lytic band of about 14 kDa. No distinct difference in the lytic activity of this enzyme was found between urchins held at two temperatures, 11 degrees and 25 degrees C. The lysozyme of this species was purified through several procedures: salting out with ammonium sulfate, precipitation by ethanol saturation, gel filtration with a Biogel column, and an affinity chromatography with a heparin Sepharose column. The combination method of Biogel filtration and affinity chromatography resulted in the most purified lysozyme fraction, but we could not obtain a single protein band in SDS-PAGE. In addition, anti-hen egg white lysozyme (HEWL) antibody was produced and confirmed to react specifically with the urchin lysozyme in this study. Therefore, the HEWL antibody may be available for examining the lytic activity of lysozyme at an individual level to determine the biodefense activity of sea urchins. Copyright 1999 Academic Press.

Journal Article↗