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Biomedical subjects

K Yamada

Publications and source records attributed to K Yamada.

At least 451 records · Page 25Linked to original sources
PubMed2000

Mitochondrial cytochrome c release and caspase-3-like protease activation during indomethacin-induced apoptosis in rat gastric mucosal cells.

Indomethacin (IND), a nonsteroidal anti-inflammatory drug, has been known to cause gastric mucosal injury as a side effect. Using a rat gastric mucosal cell line, RGM1, we determined whether apoptosis is involved in IND-mediated gastropathy, and whether caspase activation and mitochondrial cytochrome c release play an important role in producing apoptosis of IND-treated RGM1 cells in the presence of serum. IND caused caspase-3-like protease activation followed by apoptosis in a dose- and time-dependent manner. Caspase-1-like protease activity did not change during IND-induced apoptosis. IND also increased mitochondrial cytochrome c release in a time-dependent fashion. Mitochondrial cytochrome c efflux occurred just before or at the same time as caspase-3-like protease activation, and preceded the increase in apoptotic cell numbers. Z-VAD-FMK, a caspase inhibitor, inhibited both the increase in caspase-3-like protease activity and apoptosis in IND-treated RGM1 cells but did not affect caspase-1-like protease activity or mitochondrial cytochrome c release. These observations suggest that the apoptosis of gastric mucosal cells could be involved in IND-induced gastropathy, that cytochrome c is released from mitochondria into the cytosol during the early phase of IND-mediated apoptosis, and that subsequent activation of caspase-3-like protease, but not caspase-1-like protease, is required for the execution of apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Identification of Gaucher cells in the chorionic villi associated with recurrent hydrops fetalis.

Recurrent non-immune hydrops fetalis has rarely been reported. In order to detect the risk of recurrence in a subsequent pregnancy, one should carefully consider the possibility of an inborn error of metabolism. In such cases, placental examination may be useful in detecting such metabolic storage disorders in the fetus, which usually present as vacuolization of placental cells. We describe a rare case of recurrent hydrops that was detected by placental examination. Through light microscopy, electron microscope (EM) studies and beta-glucocerebrosidase activity the disease was identified as Gaucher's disease.

Adult↗
PubMed2000

Latent adenoviral infection modifies the steroid response in allergic lung inflammation.

BACKGROUND: Steroid-resistant asthma develops after adenoviral bronchiolitis. OBJECTIVE: We sought to determine the effect of steroids on allergic lung inflammation in the presence of latent adenoviral infection. METHODS: Guinea pigs with latent adenoviral (n = 12) or sham (n = 12) infections were sensitized and challenged with ovalbumin (OA) or sham sensitized and challenged with saline solution. The effect of steroids (20 mg/kg administered intraperitoneally) on OA-induced lung inflammation was examined by using quantitative histology as the outcome measure. RESULTS: Latent adenoviral infection increased CD8(+) cells in the airway wall and CD8(+) cells, macrophages, B cells, and CD4(+) cells in the lung parenchyma. Ovalbumin challenge, on the other hand, increased eosinophils, macrophages, B cells, and CD4(+) cells in both the airway wall and lung parenchyma independent of the effect of latent adenoviral infection. In the sham-infected groups steroid treatment caused the expected reduction in the eosinophilic infiltrate induced by OA challenge in the airways without affecting the other cells. In the presence of both latent adenoviral infection and OA challenge, steroid treatment had no effect on allergen-induced eosinophilia but reduced CD8(+) cells in the airways and CD8(+) cells, CD4(+) cells, and B cells in the parenchyma. CONCLUSION: Latent adenoviral infection and OA challenge result in different types of lung inflammation, and the presence of latent adenoviral infection causes OA-induced eosinophilic airway inflammation to become steroid resistant.

Adenoviridae Infections↗
PubMed2000

Effect of the 21-aminosteroid on nuclear factor-kappa B activation of Kupffer cells in endotoxin shock.

BACKGROUND: The 21-aminosteroid (U-74389G) is a nonglucocorticoid steroid that was synthesized to inhibit lipid peroxidation without the glucocorticoid activity. We recently demonstrated that the 21-aminosteroid administered to endotoxin shock mice reduces liver injury and improves the survival rate of mice through inhibition of nuclear factor-kappa B activation in the liver. The study was undertaken to determine whether the 21-aminosteroid could suppress pro-inflammatory gene up-regulation through inhibition of nuclear factor-kappa B activation in Kupffer cells. METHODS: Kupffer cells were isolated from rats by collagenase perfusion followed by pronase digestion. After a lipopolysaccharide addition, each assay was performed for tumor necrosis factor-alpha, interleukin-6, tumor necrosis factor-alpha messenger RNA, nuclear factor-kappa B, and I kappa B proteins. RESULTS: After the lipopolysaccharide addition, Kupffer cells released both tumor necrosis factor-alpha and interleukin-6. The 21-aminosteroid treatment suppressed the release of tumor necrosis factor-alpha in a dose-dependent manner. The 21-aminosteroid also inhibited the increase of tumor necrosis factor-alpha messenger RNA expression and nuclear factor-kappa B activation in Kupffer cells 1 hour and 30 minutes, respectively, after lipopolysaccharide addition. Furthermore, the 21-aminosteroid treatment suppressed the degradation of I kappa B proteins in lipopolysaccharide-stimulated Kupffer cells. CONCLUSIONS: These results suggest that the 21-aminosteroid inhibits release of the tumor necrosis factor-alpha and interleukin-6 from lipopolysaccharide-stimulated Kupffer cells by inhibiting nuclear factor-kappa B activation. This is accomplished by inhibiting I kappa B degradation in endotoxin shock and this may prove useful for the treatment of endotoxin shock.

Animals↗
PubMed2000

Long-term changes in middle latency response and evidence of retrograde degeneration in the medial geniculate body after auditory cortical ablation in cats.

Short- and long-term changes in the middle latency response (MLR) after bilateral ablation of the auditory cortices were studied in awake cats. The amplitude of the negative peak with a latency of about 15 ms (NA) decreased to 60% of the original value 1 week after ablation (short-term change). In the long term, i.e. 11-30 months, NA either decreased further (decreased group) or remained unchanged (non-decreased group). A histological study with light microscopy revealed degeneration of neurons in the ventral nucleus of the medial geniculate body (MGv) in the decreased group, whereas the neurons in this region were preserved in the non-decreased group. This study suggests that long-term changes in NA reflect retrograde degeneration in the MGv after auditory cortical ablation.

Animals↗
PubMed2000

Evaluation of pulmonary gas exchange after lobectomy and simple thoracotomy.

Postoperative influence of simple thoracotomy and lobectomy on pulmonary gas exchange was investigated in 10 patients undergoing thoracotomy and lobectomy (L group) and 10 patients with simple thoracotomy (ST group). Gas exchange was assessed with hot-wire mass spectrometry and blood gas analyses preoperatively and postoperatively at 1, 3, 6, 12, 24 and 48 h and on days 4, 6 and 13. The preoperative values of alveolar-arterial oxygen tension gradient (AaDO2), ventilation-perfusion mismatch (V(A)/Q) and circulatory shunt (Qs/Qt) were maintained in the ST group. In the L group, however, AaDO2 and Qs/Qt showed good maintenance of gas exchange for only 6-12h after lobectomy and then deteriorated because of peripheral atelectasis, resulting in poorer values than those in the ST group on days 4 and 13. Careful postoperative management, including pulmonary toilet, is essential for maintenance of gas exchange and prevention of pulmonary complications.

Adult↗
PubMed2000

Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3.

Camurati-Engelmann disease (CED [MIM 131300]), or progressive diaphyseal dysplasia, is an autosomal dominant sclerosing bone dysplasia characterized by progressive bone formation along the periosteal and endosteal surfaces at the diaphyseal and metaphyseal regions of long bones and cranial hyperostosis, particularly at the skull base. The gene for CED, or its chromosomal localization, has not yet been identified. We performed a genomewide linkage analysis of two unrelated Japanese families with CED, in which a total of 27 members were available for this study; 16 of them were affected with the disease. Two-point linkage analysis revealed a maximum LOD score of 7.41 (recombination fraction.00; penetrance 1.00) for the D19S918 microsatellite marker locus. Haplotype analysis revealed that all the affected individuals shared a common haplotype observed, in each family, between D19S881 and D19S606, at chromosome 19q13.1-q13.3. These findings, together with a genetic distance among the marker loci, indicate that the CED locus can be assigned to a 15.1-cM segment between D19S881 and D19S606.

Camurati-Engelmann Syndrome↗
PubMed2000

Promoted bone healing at a rabbit skull gap between autologous bone fragment and the surrounding intact bone with biodegradable microspheres containing transforming growth factor-beta1.

This study is a trial to promote repairing of the rabbit skull bone gap between an autologous bone flap and the intact bone with biodegradable gelatin microspheres containing transforming growth factor-beta1 (TGF-beta1). A 10-mm diameter bone defect was prepared in rabbit skulls by drilling out a bone flap of 6 mm in diameter. After a surrounding gap defect of 2 mm was created and treated with 0.5 microg of free TGF-beta1 and gelatin microspheres containing 0.5 microg of free TGF-beta1, the circular autologous bone flap was placed in the center. Significant bone healing at the gap defect was observed 3 weeks after implantation of the TGF-beta1-containing gelatin microspheres. The bone mineral density (BMD) was significantly higher than that of other experimental groups. On the contrary, when applied with free TGF-beta1, a fibrous tissue initially infiltrated into the gap defect, resulting in impairing bone healing. The tissue response was similar to that at the defect implanted with empty gelatin microspheres and TGF-beta1-free phosphate-buffered saline solution alone. There was more space in the gap-filling bone in the 16-week view than the 3-week view. It is possible that this was an intermediate step along the way toward normal healing and formation of cancellous bone. We conclude that gelatin microspheres containing TGF-beta1 show promise as an agent to promote bone regeneration of subcritical size defects between surgically positioned autologous bone flaps and surrounding host bone.

Animals↗
PubMed2000

Production of canine IFN-gamma in silkworm by recombinant baculovirus and characterization of the product.

Canine interferon-gamma (CaIFN-gamma) cDNA was expressed in silkworm by infecting recombinant baculovirus. Western blot analyses revealed that the resulting preparation contained various CaIFN-gamma protein molecules. Genetic engineering of CaIFN-gamma to remove potential glycosylation sites resulted in reduced components of the CaIFN-gamma, suggesting that one cause of this heterogeneity was glycosylation. Nonglycosylated CaIFN-gamma produced in silkworm still had several components that were deleted at the carboxy-terminal end. The major component was the CaIFN-gamma protein truncated 17 or 16 carboxy-terminal amino acid residues. CaIFN-gamma showed antiviral activity, class II major histocompatibility complex (MHC) expression-enhancing activity, and antiproliferation activity on tumor cells.

Animals↗
PubMed2000

Hypothermia modulates induction of hsp70 and c-jun mRNA in the rat brain after subarachnoid hemorrhage.

We investigated expression of hsp70 and c-jun mRNA with in situ hybridization for evaluating hypothermia effect on the brain exposed to subarachnoid hemorrhage (SAH). SAH was induced in Wistar rats with endovascular perforation. Animals were divided arbitrarily into normothermic and hypothermic groups, and they were sacrificed at 3 h or 12 h after SAH. The SAH induced hsp70 and c-jun mRNAs in the cerebral cortex, hippocampus, thalamus, hypothalamus, and caudoputamen. Mild hypothermia depressed hsp70 mRNA expression in the cortex, thalamus, and hippocampus. The c-jun mRNA expression was reduced by hypothermia in the cortex, thalamus, and CA1 of the hippocampus. Based on these findings, we speculate that hypothermia protects the brain exposed to SAH by reducing this stress response. Although it is yet difficult to employ hypothermia in the clinical settings, this study suggests its utility to those patients sustaining severe subarachnoid hemorrhage.

Animals↗
PubMed2000

Extremely low activity of methionine synthase in vitamin B-12-deficient rats may be related to effects on coenzyme stabilization rather than to changes in coenzyme induction.

Severely vitamin B-12 (B-12)-deficient rats were produced by feeding a B-12-deficient diet. The status of B-12 deficiency was confirmed by an increase in urinary methylmalonate excretion and decreases in liver B-12 concentrations and cobalamin-dependent methionine synthase activity. Rat liver methionine synthase existed almost exclusively as the holoenzyme. In B-12-deficient rats, the level of methionine synthase protein was lower, although the mRNA level was not significantly different from that of control rats. When methylcobalamin, the coenzyme for methionine synthase, was administered to the B-12-deficient rats, growth, liver B-12 concentrations and urinary excretion of methylmalonate were reversed although not always to control (B-12-sufficient) levels in a short period. During this recovery process, methionine synthase activity and its protein level increased, whereas the mRNA level was unaffected. We reported previously that rat apomethionine synthase is very unstable and is stabilized by forming a complex with methylcobalamin. Thus, the extremely low activity of methionine synthase in B-12-deficient rats may be related to effects on "coenzyme stabilization" (stabilization of the enzyme by cobalamin binding) rather than to changes in "coenzyme induction."

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2000

Role of Atf1 and Pap1 in the induction of the catalase gene of fission yeast schizosaccharomyces pombe.

We examined the induction of the catalase gene (ctt1(+)) of fission yeast Schizosaccharomyces pombe in response to several stresses by using mutants of transcription factors (Atf1 and Pap1) and a series of deletion mutants of the ctt1(+) promoter region. A transcription factor, Atf1, and its binding site are necessary for the induction of ctt1(+) by osmotic stress, UV irradiation, and heat shock. Induction by menadione treatment, which produces superoxide anion, required element A, the region from -111 to -90 (numbered with the transcription start site as +1). The factor responsible for the induction of the gene by oxidative stress via element A was identified as the transcription factor Pap1. We also found that Atf1 is activated by menadione treatment in pap1 mutant cells, although it is not activated by menadione treatment in pap1(+) cells. The activity of catalase is not increased in pap1 cells by several stresses, despite mRNA induction, suggesting that Pap1 plays some role in the expression of catalase activity.

Acetyltransferases↗
PubMed2000

NTAKalpha and beta isoforms stimulate breast tumor cell growth by means of different receptor combinations.

Neural- and thymus-derived activator for ErbB kinases (NTAK) is a recently described member of the neuregulin family that binds directly to ErbB3 and ErbB4 and transactivates ErbB2. Rat NTAK has at least five alternative-spliced isoforms: alpha1, alpha2a, alpha2b, beta, and gamma. In order to understand their biological properties, this study focused on the NTAK alpha2a and beta isoforms, which have different EGF-like domains. The effect of these isoforms on cell growth and tyrosine phosphorylation in human breast cancer cells, MDA-MB-453 and T47D, was examined using the recombinant proteins. In terms of cell growth, NTAKalpha2a and NTAKbeta preferentially stimulate T47D cells and MDA-MB-453 cells, respectively, in a dose-dependent manner. Although both NTAKs induce the highest level of tyrosine phosphorylation of ErbB2, NTAKalpha2a and NTAKbeta preferentially induce ErbB3 and ErbB4 phosphorylation, respectively. Thus, NTAKalpha2a and NTAKbeta stimulate cell growth in different ways, by means of different combinations of receptors.

Alternative Splicing↗
PubMed2000

Binding of influenza type A viruses to group B Streptococcus and haemagglutination by virus-bound bacteria.

We studied the bindings of human influenza A type viruses to group B Streptococcus (GBS), types Ia, II, III and IV, of sialic acid (SA)alpha2-3 linkage, using A/PR/8/34(H1N1) and A/Memphis/1/71(H3N2). The viruses were found to bind to all types of GBS, with the exception of PR/8/34 for GBSII, and to elute from GBSIa, III and IV at 37 degrees C, except GBSII. Electron microscopy confirmed these behaviours of the influenza viruses. The virus-binding capability of GBS types seemed to depend on the side chain length of the terminal SA. Treatment of GBSIa, III and IV, except enzyme-resistant type II, with bacterial neuraminidase resulted in the loss of virus-binding capability of GBS. These findings confirmed that SAalpha2-3 linkage of GBS capsules functions as receptor for human influenza viruses. When singular bacteria were prepared from mainly chain-like GBS with sonication, viruses were found to bind to them more efficiently. Untreated and sonicated GBS were both aggregated with high doses of virus. Furthermore, using A/Memphis/1/71(H3N2) and GBSII, we found that virus-bound GBS, untreated or sonicated, caused haemagglutination (HA). The morphological evidence that chicken erythrocytes were bridged with virus-bound native GBSII, supporting occurrences of HA, was obtained. Statistical analysis suggested that HA by virus-bound sonicated (singular) GBS was mediated by bacteria bound by at least two or three virus particles.

Animals↗
PubMed2000

Developmental regulation of a gene coding for a low-molecular-weight heat shock protein during haustorium formation in the seedlings of a holoparasitic plant, Cuscuta japonica.

Dodder (Cuscuta japonica), a holoparasitic angiosperm, develops haustoria that are essential for parasitism. We have previously demonstrated that in Cuscuta seedlings, haustorial formation could be induced efficiently by cooperative effects of far-red light and tactile stimuli in the absence of any host plant [Tada et al. (1996) Plant Cell Physiol. 37: 1049]. In this study, we performed differential display and isolated several cDNAs that were expressed differentially during haustorium development in the seedlings. Sequence similarities identified one of them as a gene encoding a 17-kDa low-molecular-weight heat shock protein (CJHSP17). Northern blot analysis revealed that CJHSP17 mRNAs constitutively accumulated in the seedlings in the absence of environmental stress, and that the transcripts dramatically decreased to undetectable levels prior to emergence of haustoria upon irradiation with far-red light in the presence of tactile stimuli. When treated with either of the two stimuli, the CJHSP17 transcript levels did not decrease and there was no differentiation of haustoria. Moreover, irradiation of red light immediately after far-red light completely repressed both the decrease of mRNAs and the subsequent formation of haustoria. These observations suggest the involvement of down-regulation of CJHSP17 in haustorium development in Cuscuta seedlings.

Amino Acid Sequence↗
PubMed2000

Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-alpha gene.

Brain levels of TNF-alpha increase in many inflammatory conditions, including HIV-1 infection, and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-alpha processing or its receptors has led us to investigate the role of TNF-alpha in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-alpha gene. Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNF-alpha-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-alpha-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-alpha-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5-infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-alpha-(-/-) mice. While the loss of TNF-alpha appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-alpha-(-/-) mice. These findings directly support a role for TNF-alpha in the neurodegenerative processes associated with viral infections such as HIV-1.

Animals↗
PubMed2000

Prophylactic administration of granulocyte colony-stimulating factor when monocytopenia appears lessens neutropenia caused by chemotherapy for lung cancer.

In a retrospective study, we showed that a monocyte count of <150/microl on days 6 to 8 might be a predictor of grade III or IV neutropenia during cancer chemotherapy given at 3- or 4-week intervals. In the present study, we investigated whether the administration of granulocyte colony-stimulating factor (G-CSF) when monocytopenia appears lessens neutropenia during chemotherapy for lung cancer. Between June 1997 and August 1998, 60 patients who received chemotherapy at 3- or 4-week intervals for unresectable lung cancer were randomized to receive G-CSF (2 microg/kg or 50 microg/m2) when monocytopenia (<150/microl) appeared on days 6 to 8 after chemotherapy (group A) or when neutropenia (<1,000/microl) or leukopenia (<2,000/ microl) appeared after chemotherapy (group B). The administration of G-CSF was stopped when the leukocyte or neutrophil counts reached > 10,000/microl or 5,000/microl, respectively. The blood cells counts were examined three times a week and the degree, duration, and frequency of chemotherapy-induced neutropenia of the two groups were compared. One patient in group A was excluded because whole brain irradiation during chemotherapy was required. Twenty-nine and 30 patients in groups A and B, respectively, received platinum-based chemotherapy and their chemotherapy-induced hematologic toxicities were analyzed. The mean neutrophil count nadir of group A (1,558 +/- 1,771/microl) was significantly higher than that of group B (810 +/- 639/microl, p = 0.032). The duration of grade III neutropenia in group A (1.4 +/- 1.7 days) was significantly shorter than that in group B (2.9 +/- 1.9 days, p = 0.004), and the frequency of grade III neutropenia in group A (48%) was significantly lower than that in group B (83%, p = 0.002). Infectious episodes occurred in five and eight patients in groups A and B, respectively. The durations of G-CSF therapy required by group A and B patients (4.8 +/- 3.1 vs. 4.7 +/- 2.7 days) were not significantly different. Prophylactic administration of G-CSF did not exacerbate anemia or thrombocytopenia induced by chemotherapy. We conclude that the prophylactic administration of G-CSF when monocytopenia appears can lessen neutropenia caused by chemotherapy for lung cancer without increasing the total G-CSF dose.

Adult↗