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Biomedical subjects

S Furukawa

Publications and source records attributed to S Furukawa.

At least 91 records · Page 5Linked to original sources

Investigation of radical reactions for efficiency improvement in ozone-hydrogen peroxide treatment.

It was verified by laboratory-scale experiments that the two-port ozone injection method was more advantageous for reaction efficiency in the ozone-hydrogen peroxide treatment than the conventional one-port ozone injection method under the condition of same ozone dose. The reason for this effectiveness was also investigated in detail by computer simulations in the wide range of the rate constant of OH radical reacting with TOC (kTOC). The laboratory-scale experiments revealed that the amount of TOC decomposed (delta TOC) increased by up to 41% by the two-port injection method, indicating a 27% improvement in delta O3/delta TOC. A detailed investigation of these experimental results by computer simulations showed that by injecting ozone in two ports the amount of ozone consumed for the OH radical formation was increased more remarkably than that of ozone consumed for the radical chain reactions, and that the amount of OH radical reacting with TOC was increased more strikingly than that with ozone. Furthermore, it was found that the smaller the kTOC value with 10(5)-10(9) M-1s-1 was, the more advantageous for the reaction efficiency the two-port injection method was.

Environmental Pollution↗

[Recurrent angina due to high grade re-stenosis of the left subclavian artery after coronary artery bypass grafting in a patient on hemodialysis for chronic renal failure: report of a case].

A 49-year-old woman on hemodialysis for chronic renal failure was admitted to our hospital with chest pain. She had undergone quadruple coronary artery bypass grafting (CABG) including a left internal thoracic to left anterior descending coronary artery anastomosis 9 months earlier. The blood flow through the left internal thoracic artery had decreased due to high grade stenosis at the proximal portion of the left subclavian artery, and recurrent angina had developed. She was treated by the placement of Palmaz biliary stents in the left subclavian artery, but re-stenosis occurred after 9 months, causing recurrent angina again. There fore, an operation was proposed and bypass grafting from the descending aorta to the left subclavian artery was successfully performed, resulting in complete resolution of her recurrent angina. This case serves to reinforce that patients on dialysis must be carefully followed up after CABG.

Angina Pectoris↗

[Delayed traumatic diaphragmatic hernia diagnosed by magnetic resonance imaging and direct coronal computed tomography: report of a case].

A 59-year-old woman was admitted to our hospital with abdominal symptoms. A diagnosis of delayed traumatic diaphragmatic hernia was made from the findings of a plain X-ray film, magnetic resonance imaging (MRI) and computed tomography (CT). We successfully performed repair of the diaphragm via abdominal approach. Thus, MRI and direct coronal CT can be very useful for establishing a diagnosis of traumatic diaphragmatic hernia.

Female↗

Reduced expression of p16 and p27 proteins in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high incidence in east Asian countries. Inactivation of cyclin-dependent kinase (CDK) inhibitors (CKIs) and overexpression of G1 cyclin has been thought to be important for tumor development. To determine whether reduction of CKI (p16 and p27) expression was associated with NPC development, we performed immunohistochemical staining of NPC specimens from 20 patients. We found that p16 and p27 proteins were negative in 8 of 20 and 16 of 20 cases, respectively; that either p16 or p27 proteins were negative in 17 of 20; and that both p16 and p27 were negative in 7 of 20. Excepting the cases in which both CKIs were negative, negativity of p27 alone was statistically higher than that of p16 (9/20 versus 1/20, P = .022), suggesting that the reduction of p27 protein is an important event for the multi-step process of NPC development.

Carcinoma, Squamous Cell↗

Increase in neurotrophin-3 expression followed by Purkinje cell degeneration in the adult rat cerebellum after spinal cord transection.

Changes in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) contents following thoracic spinal cord transection were investigated in the cerebral cortex, hippocampus, and cerebellum of rats. The NT-3 content became significantly elevated at 3 days after transection only in the cerebellum and gradually declined to the control level by 6 days after the injury, remaining unchanged in the cerebral cortex and hippocampus. No significant change in the BDNF content was observed in any of the regions tested. Immunohistochemical analysis showed that the labeling indicating NT-3-like immunoreactivity was intensified in both cerebellar granule and Purkinje cells 3 days after the injury. The number of Purkinje cells with aggregation of chromatin around the nuclear membrane and swelling of the cytoplasm and/or organelles gradually increased with time starting 4 days after the injury, demonstrating morphological changes indicative of necrosis. However, no abnormal morphology was found in cerebellar granule cells at any time examined. We suggest that it is reasonable that increased NT-3 stimulated the death of Purkinje cells, because 1) the degeneration was necrosis, which is known to be accelerated by neurotrophins under certain pathological conditions, and 2) the increase in NT-3 occurred prior to Purkinje cell degeneration. Therefore, our present results may imply that spinal cord injury-induced NT-3 accelerates injury rather than alleviates degeneration of Purkinje cells.

Animals↗

Molecular cloning and characterization of a novel gene, CORS26, encoding a putative secretory protein and its possible involvement in skeletal development.

We cloned a novel mouse cDNA, CORS26 (collagenous repeat-containing sequence of 26-kDa protein), encoding a secretory protein by suppression subtractive hybridization between transforming growth factor-beta1-treated and untreated C3H10T1/2 cells. The deduced amino acid sequence of CORS26 consists of 246 amino acids with a secretory signal peptide and contains a collagenous region (Gly-X-Y repeats) at the NH(2) terminus and a complement factor C1q globular domain at the COOH terminus. CORS26 is structurally similar to C1q and to adipocyte-specific protein Acrp30. Transfection analysis suggested that CORS26 is a secretory protein. Northern blot analysis revealed that CORS26 mRNA was present at high levels in rib growth plate cartilage and at moderate levels in kidney of adult mice. CORS26 mRNA was not detected in NIH3T3 cells, BALB/3T3 cells, C3H10T1/2 cells, or osteoblastic MC3T3-E1 cells by reverse transcription-polymerase chain reaction analysis. In situ hybridization of mouse embryos between 13 and 15 days postcoitus revealed relatively high levels of CORS26 mRNA in condensed prechondrocytic cells of cartilage primordia and developing cartilages. However, CORS26 mRNA were undetectable in mature chondrocytes. Furthermore, overexpression of CORS26 enhanced the growth of C3H10T1/2 cells in vitro. The present findings suggest that the CORS26 gene may play an important role in skeletal development.

3T3 Cells↗

Increased peripheral blood interferon gamma-producing T cells in acute disseminated encephalomyelitis.

There have been few reports on immunological studies in patients with acute disseminated encephalomyelitis (ADEM). We investigated the immunological features of ADEM using flow cytometry to examine interferon gamma (IFN-gamma)-and interleukin 4 (IL-4)-producing peripheral blood CD3+T cells from four patients with ADEM, three other neurological disorders (Fisher syndrome, epilepsy and aseptic meningitis) and 10 healthy children. IFN-gamma-producing CD3+T cells were increased in ADEM during the acute stage. In a relapsing case of ADEM, the percentages of IFN-gamma-producing CD3+T cells correlated with disease activity. There were no significant changes of IL-4-producing CD3+T cells in ADEM during the acute and convalescent stages. In conclusion, peripheral blood IFN-gamma-producing T cells are related to the pathogenesis at the early phase of the acute ADEM.

CD3 Complex↗

Abnormalities of brain perfusion in echovirus type 30 meningitis.

From May to August 1998 an epidemic of aseptic meningitis (AM) due to echovirus type 30 (E30) occurred in Yamaguchi prefecture, Japan. We performed single-photon emission-computed tomography (SPECT) to evaluate cerebral perfusion during the acute stage in 27 patients with AM due to E30. Moreover, we measured the cerebrospinal fluid (CSF) concentrations of soluble tumor necrosis factor receptor (sTNF-R) and interleukin-1 beta (IL-1beta) in all 27 patients, and the serum concentration of soluble E-selectin (sE-selectin) in 19 of the 27 patients, which is responsible for vasculitis, by means of a sandwich enzyme-linked immunosorbent assay. In 20 of the 27 (74.1%) children, SPECT imaging revealed localized cerebral hypoperfusion without abnormal focal neurological findings or symptoms. Follow-up SPECT after about 1 month revealed no abnormalities. The CSF concentrations of sTNF-R and IL-1beta, and the serum concentration of sE-selectin in the group with abnormal findings on SPECT were significantly higher than those in the group without abnormal findings on SPECT and the control subjects. Our results indicate that transient reduced regional blood flow is a frequent finding in children with AM due to E30 infection and that this abnormal finding may be induced by cerebral vasculitis.

Basal Ganglia↗

Elevated cerebrospinal fluid level of ciliary neurotrophic factor in acute disseminated encephalomyelitis.

We investigated the concentrations of ciliary neurotrophic factor (CNTF) in cerebrospinal fluid (CSF) from children with inflammatory diseases of the central nervous system. We studied 6 children with acute disseminated encephalomyelitis (ADEM), 14 with acute encephalitis/encephalopathy, 17 with bacterial meningitis, and 24 with aseptic meningitis. We found that CNTF was undetectable in the CSF of all children with acute encephalitis/encephalopathy during the acute and convalescent stages, those with aseptic meningitis, and the 25 control subjects. In children with ADEM, CNTF was undetectable during the acute stage, but its concentration was elevated in all six at the convalescent stage. In children with bacterial meningitis, the CNTF concentration was slightly elevated in two of the 17 during the acute stage and another two at the convalescent stage. Our results suggest that CNTF is part of the regulatory system for oligodendrocyte functions, such as remyelination, in ADEM.

Child↗

Dietary n-3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus.

Dietary deprivation of alpha-linolenic acid (n-3) through two generations has been shown to lower performance in an operant-type brightness-discrimination learning test in rats. Here, we examined a possible correlation between nerve growth factor (NGF) content and n-3 fatty acid status in the brain. Female rats were fed a semipurified diet supplemented with safflower oil (n-3 fatty acid-deficient) and their offsprings were fed a diet supplemented with either 3% safflower oil (Saf group) or a mixture of 2.4% safflower oil plus 0.6% ethyl eicosapentaenoate (Saf+EPA group) after weaning. The brain docosahexaenoic acid (22:6n-3, DHA) content in the Saf group was less than half of that in the Per group fed a diet supplemented with 3% perilla oil (n-3 fatty acid-sufficient) throughout the duration of the experiment. The DHA level of the Saf+EPA group was restored to the level of the Per group. However, the NGF contents in the hippocampus of the Saf and Saf+EPA groups were half that of the Per group. In the piriform cortex, the NGF content tended to be higher in the Saf and Saf+EPA groups than in the Per group. These results indicate that dietary n-3 fatty acid deficiency and restoration affect NGF levels differently among different brain regions.

Animals↗

KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells.

BACKGROUND: KRN5500, a derivative of spicamycin, shows antitumor activity against a variety of tumor cell lines. However, the mechanism of cytotoxic action has remained unclear. METHODS: The viability of HL-60 human leukemic cells treated with KRN5500 was studied by the dye exclusion assay. Induction of apoptosis and effects on the cell cycle were investigated by flow cytometry: We measured cellular DNA content after extraction of fragmented DNA, and apoptosis-induced DNA strand breaks. Cell morphology was observed by light microscopy. DNA strand breaks at a nucleosomal unit were analyzed by electrophoresis. RESULTS: Our data demonstrated that KRN5500 caused inhibition of cell growth, and that apoptosis was the mode of cell death. G(1) phase cells were more susceptible to KRN5500 induced apoptosis. In addition, KRN5500 induced cell differentiation at lower concentration. CONCLUSIONS: It is anticipated that KRN5500 will be used clinically as an anti-leukemic agent. Its mechanism of antitumor action is to induce apoptosis or cell differentiation.

Antibiotics, Antineoplastic↗

Balance of two secretion pathways of nerve growth factor in PC12 cells changes during the progression of their differentiation, with a decrease in constitutive secretion in more differentiated cells.

Proteins are secreted from animal cells by either a constitutive or a regulated pathway. When cDNA of nerve growth factor (NGF) was introduced into PC12 cells, these cells produced and secreted active NGF, where NGF was secreted not only in constitutive but also in activity-dependent regulated way according to the results of pulse-chase and ELISA studies. The regulated secretion was caused by depolarization, cyclic AMP analogue, or beta-adrenergic agonist but not by glutamate or carbachol. Because these transfected cells differentiated into a morphology indistinguishable from that incubated with NGF protein, we next compared the secretion pathways of NGF from PC12 cells at different stages of the differentiation. NGF was secreted in both constitutive and regulated way at 2 and 7 days after the transfection of NGF-cDNA, but the constitutive secretion of NGF from the more differentiated cells of Day 7 was decreased and mature NGF tended to accumulate in the cells. These results indicate that the neurotrophin secretion mechanism is intimately regulated in the course of the differentiation of PC12 cells. Such a change in the protein secretion pathway might have an profound role in the development of neurons.

Animals↗

Sodium valproate inhibits production of TNF-alpha and IL-6 and activation of NF-kappaB.

Sodium valproate (VPA) is frequently used to treat epilepsy and convulsive disorders. Several reports have indicated that anti-epileptic drugs (AED) affect the immune system, but the mechanism has not been clear. We examined whether the commonly used AEDs, diazepam (DZP), carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and VPA, can inhibit activation of the nuclear transcription factor kappa B (NF-kappaB), in human monocytic leukemia cells (THP-1) and in human glioma cells (A-172). NF-kappaB is essential to the expression of the kappa light chain of immunoglobulin and proinflammatory cytokines. Electrophoretic mobility shift assays (EMSA) of nuclear extracts demonstrated that VPA inhibits NF-kappaB activation induced by lipopolysaccharide (LPS), but the other AEDs do not. Western blot analysis revealed that this inhibition is not linked to preservation of expression of IkappaBalpha protein. Chloramphenicol acetyltransferase (CAT) assay indicated that NF-kappaB-dependent reporter gene expression is suppressed in glioma cells pretreated with VPA. VPA significantly inhibited LPS-induced production of TNF-alpha and IL-6 by THP-1 cells, whereas other AEDs did not. The findings are consistent with the idea that VPA suppresses TNF-alpha and IL-6 production via inhibition of NF-kappaB activation. Our results suggest that VPA can modulate immune responses in vitro. These findings raise the possibility that such modulation might occur with clinical use of VPA.

Anticonvulsants↗

Coding of sound-source location by ensembles of cortical neurons.

We examined the coding of sound-source location by ensembles of neurons in the auditory cortex. Broadband noise bursts were presented from loudspeakers throughout 360 degrees in the horizontal plane. Sound levels varied from 20 to 40 dB above neural thresholds. We recorded temporal spike patterns simultaneously at 16 recording sites in area A2 of alpha-chloralose-anesthetized cats. Spike patterns of individual units varied in spike counts and in spike timing as a function of sound-source location. Ensembles of up to 19 units recorded simultaneously demonstrated additional location sensitivity in the form of relative spike counts and relative spike timing among neurons. We used an artificial neural network (ANN) algorithm to recognize ensemble spike patterns and, thereby, to infer the locations of sound sources. The ANN could estimate stimulus locations based on ensemble responses to single-stimulus presentations. Median errors (MEs) averaged 49.2 +/- 11.9 degrees (mean +/- SD; n = 34; chance level, 90 degrees ). The ANN maintained better-than-chance performance even when input spike patterns were expressed as relative spike counts across units (i.e., no information available from absolute spike counts of individual units; ME, 63.0 +/- 11.8 degrees ) or when spike latencies were represented as time relative to the first spike for each trial (i.e., no external time reference available; ME, 54.3 +/- 12.4 degrees ). The ANN performance improved monotonically as the sizes of ensemble patterns were increased by combining patterns across the entire unit sample. The performance by ensembles of 128 units approached the level of localization performance of behaving cats.

Action Potentials↗

Down-regulation of antigen-specific antibody production by TCR antagonist peptides in vivo.

The efficacy of TCR antagonist peptides in inhibition of antigen-specific antibody production and T cell responses in vivo was evaluated. Among amino acid-substituted analogs of a peptide corresponding to residues 119 - 133 of bovine beta-lactoglobulin (p119 - 133), pR124Q and pD129S, prepared by substitution of Gln and Ser for Arg(124) and Asp(129), respectively, have been shown to display TCR antagonist activity for three out of four distinct p119 - 133-specific T cell clones and for polyclonal T cells derived from p119 - 133-immunized C57BL / 6 mice. Both pD129S and pR124Q inhibited in vivo priming and subsequent activation of T cells by p119 - 133 when co-injected with p119 - 133 into mice, as shown by the decreased proliferation of T cells in response to p119-133 in vitro. pD129S significantly inhibited production of anti-p119 - 113 antibodies of IgG1, IgG2b and IgE isotype in vivo when co-injected into mice together with p119 - 133 at the time of the first immunization. However, pR124Q was totally ineffective in inhibition of the antibody responses. Anti-p119 - 133 antibodies from p119 - 133-immunized mice could bind to pR124Q but not to pD129S, suggesting that the difference in cross-reactivity is responsible for the different effect of these two peptides on specific antibody production. Our findings demonstrate that a single TCR antagonist peptide can inhibit antigen-specific polyclonal antibody production when this antagonist peptide does not cross-react with the antibody elicited in response to an antigenic peptide.

Animals↗

Aberrant expression of neurotrophic factors in the ventricular progenitor cells of infant congenitally hydrocephalic rats.

OBJECTS: This study was conducted to investigate the roles of neurotrophic factors in the development of hydrocephalus in HTX rats. METHODS: Expressions of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and fibroblast growth factor (FGF)-1 were examined immunohistochemically in the cerebral cortex and ventricular zone of 6-day-old rats with congenital hydrocephalus (HTX rats). In the ventricular zone of hydrocephalic rats, potent BDNF-like immunoreactivity (-LI) and weak but significant signals for NT-3- and FGF-1-LIs were observed. However, no significant signals were detected in non-HTX rats. A small subpopulation of ventricular cells was positive for microtubule-associated protein 2 in HTX and non-HTX rats. The positive cells in the HTX rats had neurites much longer than those in the non-HTX animals, suggesting that some ventricular cells of the hydrocephalics had ectopically differentiated into mature neurons. CONCLUSIONS: This abnormal differentiation may have been responsible for the aberrant expressions of neurotrophic factors. In contrast, the cerebral neuronal layers did not show such prominent alterations in neurotrophic factor expression.

Animals↗