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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 127 records · Page 7Linked to original sources

Complications relating to intraperitoneal administration of cisplatin or carboplatin for ovarian carcinoma.

BACKGROUND: Complications associated with intraperitoneal (ip) chemotherapy is one of the factors that should be taken into consideration upon performing long-term intraperitoneal administration of chemotherapeutic agents for ovarian carcinoma. METHODS: From 1987 to 1996, 78 patients with primary ovarian carcinoma were treated with a total of 365 courses of ip administration of cisplatin (CDDP) or carboplatin (CBDCA) as a part of an initial chemotherapy regimen in combination with surgery including systematic retroperitoneal lymph node dissection using an implantable peritoneal cavity access catheter system. The complications that occurred in association with ip chemotherapy were analyzed. RESULTS: Complications associated with ip chemotherapy were seen in 27 of 78 (34.6%) patients, which included extensive intestinal adhesion, abdominal pain, local infection, ileus, bleeding at the site of implanted port, obstruction of the catheter, vaginal vault perforation, and bowel perforation. Major complications that required surgical treatment occurred in 3 patients, which included ileus, vaginal perforation, and an intestinal perforation. The perforations occurred after 18 and 36 months after the implantation of the catheter, respectively. CONCLUSIONS: It has been suggested that primary CDDP/CBDCA ip chemotherapy using an implantable catheter system can be carried out safely with rare major complications if employment of this method is restricted in 12 months after the installation of catheter.

Adult↗

Sweat gland toxicity induced by bis (tributyltin) oxide: an ultrastructural and X-ray microanalysis study.

Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secretory cells of the sweat glands. After 12 h, the secretory cells began to show intracytoplasmic edema. After 16-20 h, secretory cells in some sweat glands showed marked hydropic degeneration with swollen cytoplasm. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria of the affected secretory cells. Mitochondria dysfunction due to the toxic effects of bis (tributyltin) oxide induced changes in the secretory cells of rat sweat glands. After 24-48 h, the secretory portion of the sweat glands contained three types of cells: degenerating dark cells, regenerating cells carrying injured mitochondria, and light cells which were morphologically very similar to the cells in the transitional portion of the sweat gland. These light cells appeared to differentiate into active secretory cells after settling down in the secretory portion. Based on these observations, we concluded that the cells in the transitional portion could play an important role at least as reserve cells against secretory cell toxicity. In association with the regenerating process of the damaged secretory portions, increased mitotic activities were seen in different areas of all the dermal sweat ducts. The above-mentioned morphological observations for cell damage and subsequent regeneration and renewal ofsecretory cells in sweat gland intoxication have not been reported so far.

Animals↗

Proteasome expression in the skeletal muscles of patients with muscular dystrophy.

Previous investigators have suggested that proteolysis by calpain, a Ca2+-dependent protease, causes muscle fiber degradation in Duchenne and Becker muscular dystrophies (DMD/BMD). Recent evidence indicates that the nonlysosomal ATP-ubiquitin-dependent proteolytic complex (proteasomes) participates in muscle wasting during various catabolic states and in muscle fiber degradation in physiological or pathological conditions. To elucidate the possible role of proteasomes in dystrophic muscles, routine histochemistry and immunohistochemistry of 26S proteasomes were performed on muscle biopsy specimens obtained from patients with various neuromuscular disorders including DMD/BMD, polymyositis (PM), amyotrophic lateral sclerosis, and peripheral neuropathies, and on normal human muscle specimens. Immunohistochemically, proteasomes were located in the cytoplasm in normal human muscle, but their staining intensity was faint. Compared to control muscles, abnormal increases in both proteasomes and ubiquitin were demonstrated mainly in the cytoplasm of necrotic fibers and to a lesser extent in regenerative fibers in DMD/BMD and PM. Non-necrotic, atrophic fibers in all diseased muscles showed moderate or weak immunoreactions for the proteins; their staining intensities were stronger than those of control muscle fibers. Both proteins often colocalized well. Not all dystrophin-deficient muscle fibers showed a strong reaction for proteasomes. Our results showed increased proteasomes in necrotic and regenerative muscle fibers in DMD/ PMD, although this may not be disease-specific up-regulation. We suggest that the ATP-ubiquitin-dependent proteolytic pathway as well as the nonlysosomal calpain pathway may participate in muscle fiber degradation in muscular dystrophy.

Adolescent↗

Ictal increased writing preceded by dysphasic seizures.

Ictal increased writing has never been concretely demonstrated to be an epileptic symptom. We reported the evolution of seizures, from the beginning of reading-writing dysphasia through increased writing to secondary generalization, in a schoolchild with benign partial seizures. The lateralizing value of inter- or non-ictal hypergraphia has been stressed for the right hemisphere, while ictal increased writing most likely originated from the language area in the dominant (left) cerebral hemisphere in our patient.

Aphasia↗

Hemodynamic responses to photic stimulation in neonates.

A three-channel near-infrared monitoring system was used to evaluate the regional hemodynamic responses to photic stimulation during spontaneous sleep in seven healthy neonates. Three pairs of parallel light guides, separated by 15 mm each, were placed over a 450-mm(2) occipital region of the head. Increases in oxygenated and total hemoglobin were observed during photic stimulation only in one channel, and no change or decreases in oxygenated, deoxygenated, and total hemoglobin were observed in the other two channels. The change in the direction of deoxygenated hemoglobin accompanying the increases in oxygenated and total hemoglobin (usually a decrease in adults) differed in each subject and also varied with each measurement even in the same subject. An increase, decrease, and no change were observed. The results imply that an increase in regional cerebral blood flow occurs because of stimulation specific to the visual cortex and that the increase in deoxygenated hemoglobin observed in the visual cortex of the neonatal brain is attributable to venous dilation.

Cerebrovascular Circulation↗

T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver.

The developmental potential of individual cells in the Lin-c-kit+CD45+IL-7R+ (IL-7R+) population from murine fetal liver was investigated using a clonal assay capable of determining the potential of a progenitor to give rise to myeloid, T, and B cells. Unipotent progenitors generating T cells (p-T) or B cells (p-B) but not other types of progenitors were found in the IL-7R+ population. A large proportion of progenitors at day 12 of gestation are p-T, whereas the frequency of p-T dramatically decreases with gestational age. In marked contrast, p-B are very rare by day 12, but they rapidly increase thereafter. These findings strongly suggest that the commitment of multipotent progenitors to T and B cell lineages occurs independently.

Animals↗

Transient expression of activin betaA mRNA on osteoprogenitor cells in rat bone regeneration after drill-hole injury.

We investigated the expression of activin betaA on osteoprogenitor cells in the regenerating bone and bone marrow of the rat femur after drill-hole injury, by immunocytochemistry and in situ hybridization. The periosteum and endosteum adjacent to the wound region showed marked thickening at day 3 and abundant osteoprogenitor cells, which were immunoreactive for proliferating cell nuclear antigen and showed positive reactions for alkaline phosphatase activity, and existed in the inner layer of the periosteum as well as in the endosteum. During the same period, these osteoprogenitor cells began to exhibit activin betaA immunoreactivity and mRNA expression. However, the latter expression gradually reduced the intensity as the cells started to express osteocalcin mRNA during their differentiation to osteoblasts participating in the periosteal and medullary bone formation from day 5. Immunoreactivity for activin type IB and II receptors was also found on activin betaA-immunoreactive cells between days 3 and 7. The above findings suggest that proliferating osteoprogenitor cells, before their transformation to osteoblasts, transiently produce and release activin A, which may play crucial roles in bone and bone marrow regeneration in a receptor-mediated, autocrine and paracrine fashion.

Animals↗

Reduced early diastolic inflow velocities in the antero-posterior transverse direction in the left ventricle of patients with dilated cardiomyopathy.

UNLABELLED: In patients with dilated cardiomyopathy (DCM), the left ventricular (LV) inflow jet is narrow and has a high pressure gradient. A pulsed Doppler restrictive transmitral flow pattern is a characteristic feature of severe left ventricular disease. However, Doppler flow analysis is limited by the angle between the blood flow jet and the ultrasonic beam. In this study we used gated magnetic resonance imaging (MRI) to investigate the inflow velocity in the LV transverse directions during early diastole in patients with DCM. METHODS: We studied 10 patients with DCM (mean age: 47 y). Ten age-matched healthy volunteers were also examined. Gradient echo images of the LV were obtained. Left ventricular short axis phase contrast images were obtained at the level of the mitral valve tip and 1 cm inside the LV. Long axis images were also obtained. Through-plane peak velocities at peak early diastolic filling were measured along the LV long axis, antero-posterior short axis, and right-left short axis. Blood velocity was measured in 50 ms blocks. RESULTS: Early diastolic inflow velocity along the long axis, especially at the center of the LV, was well preserved in DCM. However, the inflow velocity in the antero-posterior transverse direction of the LV (i.e., in the direction of mitral valve excursion) was significantly reduced in DCM. CONCLUSIONS: Early diastolic inflow velocity in the antero-posterior transverse direction of the LV is reduced in patients with DCM indicating that the vector component of the forces acting in the antero-posterior transverse direction of the LV may be decreased in patients with DCM during early diastolic filling.

Adult↗

The insulinotropic mechanism of the novel hypoglycaemic agent JTT-608: direct enhancement of Ca(2+) efficacy and increase of Ca(2+) influx by phosphodiesterase inhibition.

We examined the effects of the novel hypoglycaemic agent JTT-608 [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid] on insulin secretion using rat pancreatic islets, and analysed the mechanism of its effect. JTT-608 augmented 8.3 mM glucose-induced insulin secretion dose-dependently, and there was a stimulatory effect of 100 microM JTT-608 at both moderate and high concentrations (8.3, 11. 1 and 16.7 mM) of glucose, but not at low concentrations (3.3 and 5. 5 mM). In perifusion experiments, both phases of insulin release were enhanced, and the effect was eliminated 10 min after withdrawal of the agent. In the presence of 200 microM diazoxide and a depolarizing concentration (30 mM) of K(+), there was an augmentation of insulin secretion by 100 microM JTT-608, not only under high levels of glucose but also under low levels, and the effects were abolished by 10 microM nitrendipine. JTT-608 augmented insulin secretion from electrically permeabilized islets in the presence of stimulatory concentrations (0.3 and 1.0 microM) of Ca(2+), and the intracellular Ca(2+) concentration ([Ca(2+)](i)) response under 16.7 mM glucose, 200 microM diazoxide, and 30 mM K(+) was also increased. The cyclic AMP content in the islets was increased by 100 microM JTT-608, and an additive effect to 1 microM forskolin was observed, but not to 50 microM 3-isobutyl-1-methylxanthine (IBMX). JTT-608 inhibited phosphodiesterase (PDE) activity dose-dependently. We conclude that JTT-608 augments insulin secretion by enhancing Ca(2+) efficacy and by increasing Ca(2+) influx. This appears to be a result of the increased intracellular cyclic AMP concentration due to PDE inhibition.

Animals↗

Postpartum thyroid dysfunction in women with normal thyroid function during pregnancy.

OBJECTIVE: The aim of this study was to establish the risk of postpartum thyroid dysfunction (PPTD) in women who had normal thyroid function during pregnancy and no history of thyroid disease. DESIGN: Four thousand and twenty-two consecutive pregnant women were screened for thyroid function and antithyroid antibody. Among women with normal thyroid function during pregnancy and no history of thyroid disease, thyroid function were assessed in 131 of 388 antithyroid antibody positive (Group I) and 1030 of 3503 antibody negative (Group II) women at 1 and 3 months postpartum. In Group I women who experienced PPTD, the frequency of later manifestation of Hashimoto's disease was compared according to titres of antithyroid antibodies. MEASUREMENTS: Blood samples in early pregnancy, and at 1 month and 3 months postpartum were obtained using the dried blood spot method. Levels of fT4 were measured by RIA, TSH by fluoroimmunoassay or ELISA, antimicrosome antibody (AMC) and antithyroglobulin antibody (ATG) by indirect agglutination reactions. RESULTS: The prevalence of PPTD at 1 month and 3 months postpartum were found to be 6.9% and 21.3% in Group I, and 5.3% and 4.7% in Group II, respectively. The prevalence of PPTD was significantly higher at 3 months postpartum in Group I (P<0.05). 27.3% of women with PPTD in Group I were later found to have Hashimoto's disease and 9.1% manifested hypothyroidism without goitre. A high AMC titre (> or = 25600) at 3 months postpartum in women with PPTD was related to the manifestation of Hashimoto's disease. AMC titres of PPTD women and women who developed Hashimoto's disease were significantly higher than those of control women who did not experience PPTD. CONCLUSION: A high prevalence of PPTD was found in women with antithyroid antibodies who were euthyroid during pregnancy. Prolonged follow-up of the subsequent thyroid function may be needed in women who experience PPTD and/or show a high titre of antithyroid antibody.

Autoantibodies↗

Dietary zinc deficiency decreases glutathione S-transferase expression in the rat olfactory epithelium.

Zinc deficiency leads to olfactory and gustatory dysfunction, but little is known about the underlying molecular mechanism of this phenomenon. We examined the effect of dietary zinc deficiency on the rat olfactory epithelium. Immunoreactivities of glutathione S-transferase (GST) mu, neuron-specific enolase (NSE) and proliferating cell nuclear antigen (PCNA), and in situ hybridization of GST mu mRNA in the olfactory epithelia were examined under different dietary zinc intake conditions. Adult male rats were fed a zinc-deficient (ZD) diet (0.5 mg zinc/kg diet), whereas control rats, including pair-fed (PF) and zinc-adequate (ad libitum consumption, AL) groups, were fed a zinc-adequate diet (58 mg zinc/kg diet) for 7 wk. We also examined the effect of zinc replacement (ZR) by subsequently feeding half of the ZD group a zinc-adequate diet for 5 wk after the initial 7-wk deprivation. No significant differences in immunoreactivity for NSE in olfactory epithelial receptor cells or for PCNA in basal cells were noted among groups. Intense GST mu immunoreactivity and hybridization signals were observed in olfactory supporting cells of AL, PF and ZR groups, but very minimal or no such signal was noted in ZD rats. Our findings indicated that zinc deficiency reduces GST mu expression in the supporting cells of rat olfactory epithelia but does not affect receptor cell proliferation or maintenance.

Actins↗

Release of membrane vesicles containing endotoxic lipopolysaccharide in Escherichia coli O157:H7 clinical isolates.

Membrane vesicles released by E. coli O157:H7 strains were investigated by immuno-electron microscopy using anti-O157 antibody. Anti-O157 antibody enhanced the negative-staining of vesicles and we found numerous small vesicles clearly formed around bacterial cells. An immunogold-electron microscopic examination confirmed that lipopolysaccharide (LPS) including the O-side chain is present on the surface of the vesicles. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the purified vesicles showed that the vesicles contained LPS consisting of a lipid-A and an O polysaccharide. In addition, the endotoxic activity of the vesicle was confirmed by a limulus test. These results suggest that the vesicles may play an important role in the pathogenesis of Escherichia coli O157:H7.

Animals↗

Prevention of vaginal shortening following radical hysterectomy.

We describe a surgical procedure and post-operative management for the prevention of vaginal shortening following radical hysterectomy. A total of 452 patients who underwent hysterectomies were examined prospectively depending on the operation method. This study showed that our procedure was effective in the prevention of vaginal shortening following radical hysterectomy. Preservation of the ovaries appeared to be important in preventing vaginal shortening, and post-operative hormone replacement therapy was not as effective as the preservation of the ovaries. The effect of external irradiation on vaginal shortening was not conspicuous in the case that the ovaries were preserved.

Adolescent↗

Restriction fragment length polymorphism analysis using random chromosomal gene probes for epidemiological analysis of Campylobacter jejuni infections.

We have evaluated the ability of a new genotyping method for Campylobacter jejuni based on restriction fragment length polymorphisms using random chromosomal gene probes. DNAs from C. jejuni strains digested with each of three restriction enzymes, HhaI, HaeIII, and HpaII, were analyzed by Southern hybridization using each of two unrelated cosmid clones, P14 and P15 (respectively containing 30- and 35-kb genomic DNA fragments of C. jejuni strain OH4384). The method reported provides a stable and discriminating means for identifying C. jejuni strains and should be useful for epidemiological analyses.

Bacterial Typing Techniques↗

Augmentation of basal insulin release from rat islets by preexposure to a high concentration of glucose.

We have found that preexposure to an elevated concentration of glucose reversibly induces an enhancement of basal insulin release from rat pancreatic islets dependent on glucose metabolism. This basal insulin release augmented by priming was not suppressed by reduction of the intracellular ATP or Ca(2+) concentration, because even in the absence of ATP at low Ca(2+), the augmentation was not abolished from primed electrically permeabilized islets. Moreover, it was not inhibited by an alpha-adrenergic antagonist, clonidine. A threshold level of GTP is required to induce these effects, because together with adenine, mycophenolic acid, a cytosolic GTP synthesis inhibitor, completely abolished the enhancement of basal insulin release due to the glucose-induced priming without affecting the glucose-induced increment in ATP content and ATP-to-ADP ratio. In addition, a GDP analog significantly suppressed the enhanced insulin release due to priming from permeabilized islets in the absence of ATP at low Ca(2+), suggesting that the GTP-sensitive site may play a role in the augmentation of basal insulin release due to the glucose-induced priming effect.

Adenosine Triphosphate↗

Factor XII deficiency in women with recurrent miscarriage.

Congenital thrombophilia is known to cause significant maternal complications, and possibly has an adverse effect on normal fetal development. The aim of this study was to assess the prevalence of factor XII (FXII) deficiency in women with a history of recurrent miscarriage. Two hundred and forty-one consecutive Japanese women with a history of two or more recurrent miscarriages were prospectively assessed for their etiology by conventional screening methods. Seven women were found to have reduced FXII activity (19. 2-46.1%) and prolonged activated partial thromboplastin time (33. 3-51.3 s). Of these 7 women, 6 had experienced early pregnancy losses, while 1 woman had experienced repeated mid-trimester fetal losses with coincidental gestational thrombocytopenia. In 241 women with a history of recurrent miscarriage, the prevalence of FXII deficiency was 2.9%.

Abortion, Spontaneous↗

Effects of inflammatory cytokines on prostaglandin E(2) production from human amnion cells cultured in serum-free condition.

The effects of five inflammatory cytokines, i.e. interleukin(IL)-1alpha, IL-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) on prostaglandin E(2) (PGE(2)) production from amnion cells cultured in a serum-free condition was evaluated. After human amnion cells obtained from term placenta were incubated with the inflammatory cytokines at various concentrations, PGE(2) production in the culture supernatant was determined using an enzyme immunoassay method. Under a serum-free culture condition, an increase in PGE(2) production by IL-1alpha and IL-1beta was observed at concentrations of 10 and 100 ng/ml compared to control cultures. However, the increases in PGE(2) production by IL-6 and IL-8 were found at relatively high concentrations, i.e. at 100 and 200 ng/ml. TNF-alpha induced a significant increase in PGE(2) production at 50 and 100 ng/ml, but not at 200 ng/ml. These data suggest that these inflammatory cytokines directly stimulate PGE(2) production from amnion cells and may initiate premature labor if amniotic inflammatory cytokines are elevated, e.g. following intrauterine infection.

Adult↗