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Biomedical subjects

K Fujisawa

Publications and source records attributed to K Fujisawa.

At least 37 records · Page 2Linked to original sources

Evaluation of cellular adhesions on silicone and poly(methyl methacrylate) intraocular lenses in monkey eyes: an electron microscopic study.

PURPOSE: To assess the biocompatibility of intraocular lens (IOL) material by studying the number of cells adhering to IOLs in monkey eyes. SETTING: Department of Ophthalmology, Kyushu University, Fukuoka, Japan. METHODS: Silicone or poly(methyl methacrylate) (PMMA) IOL implantation was performed in 21 monkeys. One eye of each animal had surgery. The IOL-implanted eyes were enucleated 1, 2, 3, 5, and 7 days and 1, 3, 4, 5, and 9 months after the procedure. One eye was studied at each time. Cells on the anterior IOL surface were photographed using a scanning electron microscope, counted and assessed with NEC, Graphtec, and Nikon equipment, and then observed using a transmission electron microscope. RESULTS: Leukocytes, macrophages, and giant cells were found on the anterior IOL surface. Numerous cells were observed on the PMMA IOLs in the early postoperative period; they gradually decreased. Few cells were seen on the silicone IOLs during the course of the study. The giant cells became larger during the postoperative period. CONCLUSION: The foreign-body reaction to silicone IOLs in monkey eyes was less than that to PMMA IOLs.

Animals↗

An autopsy case of hemilaterally dominant and systematic/extensive border zone infarction: sequela of preceding atherosclerotic obstruction of one common carotid artery followed by repeated episodes of systemic hypotension.

A 68-year-old man was admitted to St Marianna University Hospital on account of loss of consciousness with left hemiplegia. During the hospital recovery course with a rehabilitation procedure, the patient's blood pressure was very unstable, fluctuating between high (210/110 mmHg) and low (110/70 mmHg) values accompanied by a fainting sensation. A second stroke of left hemiplegia took place 1 month later. Afterwards, his condition worsened to tetraplegia with dysarthria. Three months later, lung cancer with multiple metastasis including his left neck was found and he died from adynamic ileus 6 months after the onset of the present illness. Autopsy revealed nearly complete atheromatous obstruction and more than 50% stenosis, respectively, of his right common and internal/external carotid arteries. His intracranial arterial trunks and main branches were all patent with localized atherosclerosis of only moderate degree. The pathology of the brain existed predominantly in the right hemisphere in the border zone area between the anterior and middle cerebral arteries systematically with numerous disseminated foci of complete or incomplete necrosis, white matter and gray matter being involved independently. Involvement of centrum semiovale white matter is more extensive and intensive than that of gray matter. Of the gray matter, cerebral cortex as well as striatum, periventricular (the third ventricle) gray and cerebellar cortex was involved. The specific characteristic topography and distribution of the lesions together with their histopathology are described in detail with illustration. It is concluded that this case represents an outstanding example of hemodynamic cerebral circulatory insufficiency doubly caused by hemilateral carotid artery stenosis and repeated episodes of systemic hypotension.

Aged↗

Effects of interleukin-4 on the in-vitro production of cytokines by human endometrial stromal cells.

A T helper (Th)1/Th2 model has been applied to as a system regulating the cytokine network during pregnancy. To evaluate the effects of interleukin (IL)-4, a Th2 cytokine, on the cytokine production by endometrial stromal cells (ESC), an enzyme-linked immunosorbent assay was used to measure the concentrations of IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage colony-stimulating factor (M-CSF) in the culture media of ESC and of an endometrial stromal sarcoma cell line, MaMi, following the addition of recombinant human IL-4. The expression of mRNAs for IL-6 and IL-8 in ESC after stimulation with IL-4 was also evaluated by Northern blot analysis. Increases in the concentrations of IL-6, IL-8, MCP-1, and M-CSF in the culture media of ESC and MaMi cells were observed on the addition of increasing amounts of IL-4. This cytokine also stimulated the transcription of IL-6 and IL-8 in ESC in a dose-dependent manner. It is suggested that IL-4 secreted by the maternal decidual tissue as well as by the developing embryo may stimulate the production of IL-6, IL-8, MCP-1, and M-CSF by ESC. The increased concentration of these cytokines in the local environment may contribute to the maintenance of early pregnancy by modulating the immune reaction at the feto-maternal interface.

Animals↗

Expression of epithelial neutrophil-activating peptide 78 in cultured human endometrial stromal cells.

It has been demonstrated that human endometrial stromal cells (ESC) produce a variety of chemokines in vivo and in vitro. To evaluate the expression of epithelial neutrophil-activating peptide 78 (ENA-78) in the endometrium, concentrations of ENA-78 in cyclic endometrial tissues were measured using enzyme-linked immunosorbent assay. The expression of ENA-78 was also detected in cyclic endometrium by immunohistochemistry. Endometrial tissues in the secretory phase contained higher amounts of ENA-78 protein than did those in the proliferative phase. Immunofluorescence staining revealed that ENA-78 protein was localized mainly in the stroma of endometrium. In addition, to evaluate the involvement of inflammatory mediators and ovarian steroid hormones in the production of ENA-78 by ESC was evaluated by in-vitro studies. Unstimulated ESC constitutively secreted ENA-78. Progesterone, lipopolysaccharide, tumour necrosis factor-alpha, and interleukin-1beta significantly stimulated the expression of ENA-78 by ESC. It is suggested that the production of ENA-78 by ESC is regulated by progesterone as well as by the inflammatory mediators. The modulation of ENA-78 concentration in the local environment by these mediators may contribute to the normal and pathological processes of human reproduction through regulation of leukocyte trafficking into the endometrium.

Cells, Cultured↗

Effects of platelet-activating factor on cytokine production by human uterine cervical fibroblasts.

Platelet-activating factor (PAF), a lipid that acts as a potent proinflammatory mediator, is involved in several reproductive processes including parturition. To investigate the effects of PAF on expression of various cytokines by cultured human uterine cervical fibroblasts obtained at term prior to labour, Northern blot analyses and enzyme-linked immunosorbent assays were performed. C-PAF, a stable analogue of PAF, increased expression of interleukin-6 and -8 mRNA in a dose-dependent manner (10(-10) to 10(-8) mol/l of C-PAF), and the expression peaked within 4 h. The corresponding protein concentrations were increased in culture media. Monocyte chemoattractant protein-1 mRNA showed marked induction by 10(-8) mol/l of C-PAF; this peaked by 4 h and was followed by an increase in the protein concentration. Another cytokine, RANTES (regulated upon activation, normal T cell expressed and secreted) showed marked mRNA induction by 10(-8) mol/l of C-PAF, and continued to increase in a time-dependent manner until 24 h. The protein concentration was correspondingly increased in the medium. The PAF-induced cytokine production was abolished by co-incubation with WEB 2170, a specific PAF receptor antagonist. PAF may stimulate local production of cytokines which may induce migration of leukocytes and accelerate collagenolysis in the uterine cervix, thus contributing to cervical ripening during parturition.

Cells, Cultured↗

Expression and regulation of growth-regulated oncogene alpha in human endometrial stromal cells.

Growth-regulated oncogene alpha (GROalpha), a potent chemoattractant for neutrophils, has previously been detected in the endometrial stromal cells (ESC) of human endometrium. In this study, the mRNA expression of GROalpha in the endometrium was evaluated by reverse transcription-polymerase chain reaction analysis, while the localization of GROalpha protein was studied by immunohistochemistry and the concentrations of GROalpha were measured using an enzyme-linked immunosorbent assay (ELISA). The effects of known modulators of endometrial function on the production of GROalpha by ESC were also examined by ELISA and Northern blot analysis. The expression of both GROalpha mRNA and GROalpha protein was detected in the cycling endometrium. GROalpha protein was localized mainly in the stroma, and endometrial tissues in the secretory phase contained higher amounts of GROalpha protein than did those in the proliferative phase. The production of GROalpha by ESC was enhanced by in-vitro decidualization. Lipopolysaccharide, tumour necrosis factor-alpha and interleukin-1beta also stimulated the expression of GROalpha mRNA and protein by ESC. These results suggest that the production of GROalpha by ESC is regulated by ovarian steroid hormones as well as by inflammatory mediators. The modulation of GROalpha concentrations in the local environment may contribute to normal and pathological processes in the uterus by regulating leukocyte trafficking in the endometrium.

Cells, Cultured↗

Involvement of thioredoxin in the regulation of growth hormone secretion in rat pituitary cell cultures.

We report here an examination of the effect of thioredoxin (TRX) on the secretion of growth hormone (GH) from rat anterior pituitary cells in vitro. Treatment of rat pituitary cells with growth hormone-releasing factor (GRF), but not GH, led to a significant increase in intracellular TRX protein levels. GRF, recombinant human TRX (rhTRX), and a combination thereof were all shown to induce immediate GH secretion from pituitary cells, as evidenced by perifusion experiments. RhTRX, but not other reducing agents such as beta-mercaptoethanol and N-acetyl-L-cysteine, augmented GRF-stimulated and -unstimulated GH secretion from rat pituitary cells in a dose-dependent manner. RhTRX did not significantly affect the GH mRNA expression of pituitary cells stimulated in the presence or absence of GRF. In addition, rhTRX-augmented GH secretion was not significantly affected by the presence of cycloheximide. Collectively, these findings suggest that TRX is induced by stimulation with GRF and plays a regulatory role in GH secretion from rat anterior pituitary cells by enhancing the secretion of stored GH, rather than by the synthesis of GH.

Animals↗

Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis.

BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Angiotensin-Converting Enzyme Inhibitors↗

An adult case of congenital external carotid-jugular arteriovenous fistula with reversible circulatory insufficiency in the cerebellum and lower brain stem.

A 27-year-old man with congenital external carotid-jugular arteriovenous fistula presented with a diminished level of consciousness and an ataxic gait. Axial fluid-attenuated inversion-recovery (FLAIR) MR imaging revealed venous congestion, a dilated right jugular vein, and an area of high signal intensity in the brain stem and cerebellum. Angiography showed a dilated right external carotid artery and jugular vein and the presence of a fistula. After coil embolization of the fistula, axial MR FLAIR images showed only a few areas of high signal intensity in the brain stem and cerebellum. The causal factor was venous congestion in the inferior petrosal sinus and basilar plexus due to high blood pressure in the jugular vein. This case is presented for its unusual clinical and radiologic findings.

Adult↗

[Influence of cyclosporin on steroid-induced cataract].

PURPOSE: To study the effect of cyclosporin on steroid-induced cataract in patients after renal transplantation. SUBJECTS AND METHODS: 140 patients who received renal transplantation and ophthalmological examinations before and over 12 months after surgery at Kanazawa Medical University were investigated retrospectively. The subjects were divided into the following two groups: the conventional therapy group(Group C) who were administered azathioprin and methylprednisolone and the triple therapy group(Group T) who were administered azathioprin, methylprednisolone and cyclosporin. There were 73 subjects in group C and 67 in group T. Judgement of steroid cataract followed Crew's classification and steroid cataract was diagnosed when vacuoles or opacity were seen in the posterior subcapsular region. Subjects that had any lens opacity before renal transplantation were excluded. RESULTS: The total dose of systemic steroid during the first year and in the final observation period in group T was significantly higher than in group C. The prevalence of steroid cataract was 55% and 63% for the 1st year, 72% and 89% for the 2nd year, 74% and 92% for the 3rd year and 83% and 96% for the 5th year in groups C and T, respectively. By the third year, the rate of subjects whose corrected visual acuity was less than 0.8 or who received cataract surgery was significantly higher in group T than in group C. There was no significant difference in the total dose between the subjects with cataract over grade I and those of grade 0 and I in both groups C and T. In group C, the total dose of steroid pulse therapy was significantly higher in the subjects with steroid cataract over grade I than in those with grade 0 and I. CONCLUSIONS: Using cyclosporin, although the total dose of systemic steroid was decreased, the rate of steroid cataract increased. Cyclosporin may accelerate the development of steroid cataract. Steroid pulse therapy is considered to be a risk factor for developing steroid cataract.

Adolescent↗

Expression of c-Ets1 is associated with malignant potential in endometrial carcinoma.

BACKGROUND: The protooncogene c-ets1 is a transcriptional factor that controls the expression of a number of genes involved in extracellular matrix remodeling. It might play a role in the regulation of physiologic processes such as cell proliferation and differentiation and also is associated with angiogenesis, cell migration, and tumor invasion. METHODS: To elucidate the involvement of c-Ets1 in endometrial carcinogenesis, the authors analyzed serial frozen sections for c-Ets1 protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. The authors analyzed the relation between the percentages of c-Ets1 stained cells and patient characteristics including histologic grade, surgical stage, presence of invasion to greater than one-half myometrium, presence of vascular involvement, presence of lymph node metastasis, and clinical outcome. RESULTS: In the normal endometria, c-Ets1 was weakly detected at the luminal surface of endometrial glands in both the proliferative and secretory phases. Most of the c-Ets1 proteins were found in the cytoplasm and partly in the nucleus of endometrial carcinoma glands, and also in fluid secreted from endometrial carcinoma glands. Moreover, c-Ets1 was strongly expressed in the head portion of papillary carcinoma tissues that invaded the stroma. c-Ets1 expression was associated significantly with histologic grade (P < 0.005), the presence of invasion to greater than one-half myometrium (P < 0.001), surgical stage (P < 0.005), and vascular involvement (P = 0.009). CONCLUSIONS: The authors' results show that c-Ets1 expression in endometrial carcinoma correlates with the malignant potential of this tumor.

Endometrial Neoplasms↗

cDNA cloning and chromosomal mapping of the gene encoding adenylate kinase 2 from Drosophila melanogaster.

As a step toward understanding of the role of adenylate kinase (AK) in energy metabolism, we analyzed this enzyme in Drosophila melanogaster. The enzyme activities of all three AK isozymes were determined in cell-free extracts of flies, and their proteins were detected by Western blot analysis using polyclonal antibodies against the mammalian isozymes. A cDNA encoding adenylate kinase was isolated from D. melanogaster cDNA library. The cDNA encodes a 240-amino acid protein, which shows high similarity to bovine, human and rat AK2, and hence was named DAK2. Preliminary subcellular fractionation analysis indicated that DAK2 is localized in both cytoplasm and mitochondria. In situ hybridization to salivary gland polytene chromosomes revealed that the Dak2 gene is located at 60B on the right arm of the second chromosome.

Adenylate Kinase↗

Adenovirus-mediated viral IL-10 gene transfer prolongs survival of xenogeneic spheroidal aggregate-cultured hepatocytes.

Xenotransplantation of hepatocytes appears to be a novel promising therapy for some forms of liver disease, and may well overcome the problem of donor shortage. We have previously reported that hepatocytes with a spheroidal shape (spheroids) are ideal for cell transplantation. The application of gene transfer techniques to this hepatocyte transplantation could possibly regulate the xenogeneic rejection reaction and, therefore, result in prolongation of the survival of the transplanted hepatocytes. In this study, we chose the adenovirus as a vector and an immunosuppressive cytokine named viral IL-10 (vIL-10) for transfection. A series of experiments was performed to elucidate the efficacy of transfection to the spheroids with adenovirus vectors and the effect of transfected vIL-10 on the survival of xenogeneic hepatocytes. We examined the cell survival quantitatively by evaluating beta-galactosidase (beta-gal) activity, which was transfected into the hepatocytes in the xenogeneic spleen, and semiquantitatively by the histological findings. The results of in-vitro studies identified an efficient expression of the beta-gal gene within the spheroids infected with Ad-CMVLacZ (LacZ-encoding adenovirus vector with CMV promotor) and the presence of BCRF1 mRNA within the spheroids transfected with AdCMVvIL-10 (vIL-10-expressing adenovirus vector with CMV promotor) under the condition of 1 MOI, for 1 h. Xenogeneic hepatocytes with a spheroidal shape showed comparable survival to syngeneic hepatocytes for up to 4 days after transplantation with co-transplantation of the vIL-10-transfected hepatocytes. From this study, we concluded that adenovirus-mediated vIL-10 gene transfer prolongs the survival of xenogeneic hepatocyte spheroids. Furthermore, spheroids possess ideal properties for gene transfection, as well as cell transplantation.

Adenoviridae↗

Intracranial hemorrhage in children with immune thrombocytopenic purpura

We sent questionnaires to hospitals in Japan in order to study the incidence and conditions of intracranial hemorrhage (ICH) in children with immune thrombocytopenic purpura (ITP). From 1980 to 1995, 11 cases of ICH were reported in eight patients with ITP at 35 institutions. One patient had ICH four times, but only one patient died of the condition. From 1990 through 1995, ICH occurred in four (0.52%) of 772 patients with ITP. None of the patients died. The platelet count when ICH occurred was 5.2 +/- 3.7 x 10(9)/l (mean +/- SD) (n = 11). Four of the eight patients (1980-1995) had received active treatment [e.g. intravenous immunoglobulin G (i.v. IgG)] immediately before ICH occurred. In seven cases (1980-1995), possible causes of ICH, including menstruation (n = 2) and viral infections (n = 3), were identified. Systemic lupus erythematosus (SLE) later developed in three patients. Although the incidence of ICH in children with ITP has not decreased compared with the rates in earlier studies, the mortality rate has decreased markedly. Our results suggest that menstruation, infection, and risk factors for progression to SLE may help to predict ICH in children with ITP. Large-scale prospective trials are needed to identify risk factors for ICH.

Acute Disease↗

Generalized peritonitis due to spontaneously perforated pyometra presenting as pneumoperitoneum: report of a case.

We report a rare case of generalized peritonitis due to a ruptured pyometra in an 86-year-old woman, and also conduct a review of the previous Japanese literature. The patient presented with muscle guarding and rebound tenderness. Computed tomography (CT) disclosed a cystic mass in the peritoneal cavity, in which an air-fluid level was noted. Pneumoperitoneum around the uterus due to gas production of anaerobic bacteria was noted on a CT. At laparotomy, the uterus was markedly enlarged with a necrotic area on the uterine fundus, which was found to be perforated. A supravaginal hysterectomy and drainage were performed. We found only eight cases of a ruptured pyometra presenting as pneumoperitoneum in the Japanese literature between 1977 and 1999. The most common cause of pneumoperitoneum is a perforation of the gastrointestinal tract. However, other possible causes, as seen in our patient, should also be taken into consideration. Although it is rare, a perforated pyometra should therefore also be considered when elderly women present with acute abdominal pain.

Aged↗