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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 163 records · Page 9Linked to original sources
PubMed1998

The requirement of intercellular adhesion molecule-1 for neutrophil respiratory burst in the pulmonary circulation of rats infused with endotoxin.

Recently, we demonstrated direct evidence of respiratory burst of the neutrophil in the pulmonary circulation of the endotoxin-infused rat (Am. J. Respir. Crit. Care Med. 1995;152:348-354). To determine the role of intercellular adhesion molecule-1 (ICAM-1) in this model, we neutralized ICAM-1 using antirat ICAM-1 monoclonal antibody (mAb) 1A29. We observed and measured the number of sticking leukocytes and the amount of hydrogen peroxide (H2O2) in the pulmonary circulation of the endotoxin-infused rat by means of a fluoro-imaging technique. The rats received 4.5 mg/kg/h of endotoxin for 2 h. Ten rats received 2 mg/kg of mAb 1A29 20 min before the intravenous infusion of endotoxin. Although the pretreatment with mAb 1A29 did not reduce the number of leukocytes sticking to the pulmonary capillaries, it almost completely inhibited the H2O2 production of leukocytes in the rat lung infused with endotoxin. We confirmed that the leukocytes that produced H2O2 were neutrophil by an electron microscopic cerium technique. We conclude that, although ICAM-1 is not necessary for neutrophil to stick to the capillary in the rat pulmonary circulation infused with endotoxin, ICAM-1 is required for neutrophil H2O2 production in this model.

Animals↗
PubMed1998

Platelet-activating factor mediates intercellular adhesion molecule-1-dependent radical production in the nonhypoxic ischemia rat lung.

It has been reported that reperfusion is the most important factor in ischemia-reperfusion (I/R) injury. However, causes of I/R injury in the lung are controversial, because oxygen is always supplied if ventilation continues. Therefore, we hypothesized that nonhypoxic ischemia without reperfusion is sufficient for lung injury. To test our hypothesis, we measured both hydrogen peroxide (H2O2) production in the pulmonary circulation, by digital imaging fluorescent dichlorofluorescein, and microvascular permeability (MVP), by the Evans blue extravasation technique in the nonhypoxic ischemia rat lung. We made a nonhypoxic ischemia rat lung by clamping the left pulmonary artery. Both H2O2 production and MVP increased in the nonhypoxic ischemia rat lung. We also determined the effect of oxygen removal by clamping the bronchus in advance of pulmonary artery occlusion, intercellular adhesion molecule-1 (ICAM-1) neutralization with monoclonal antibody 1A29, and platelet-activating factor (PAF) receptor antagonist CV6209 on H2O2 production and MVP. These treatments inhibited both H2O2 production and MVP increase. At high-power viewing of the fluorescent dichlorofluorescein image, H2O2 was detected in the leukocytes within pulmonary capillaries. These data indicate that the nonhypoxic ischemia without reperfusion alone causes radical production and increases MVP. Furthermore, PAF and ICAM-1 contribute to these reactions.

Animals↗
PubMed1998

[Direct effects of Chinese herbal medicine "hochuekkito" on sperm movement].

BACKGROUND AND PURPOSE: Chinese herbal medicine, "Hochuekkito" is widely used for male infertility in Japan. There have been many reports concerning its clinical usefulness but very few reports of in vitro experiments studying the mechanism of its effects. In addition to stimulating germ cells, we analyzed its direct effects on sperm using computer assisted semen analyzer (CASA). MATERIALS AND METHODS: Motile sperm were prepared using swim up technique from semen collected from ten healthy volunteers. Sperm movements (motility, velocity, linearity) were analyzed by CASA after adding either serum containing anti-sperm antibody (ASA) or normal serum with or without Hochuekkito. RESULTS: Two hours after adding serum with ASA, the decrease of sperm motility was significantly reduced from 25.1% (92.8%-->67.7%) to 12.5% (92.9%-->80.6%) by adding Hochuekkito. No significant difference in velocity and linearity was observed between two groups. By adding normal serum, any of three parameters differed significantly with or without Hochuekkito. CONCLUSION: Protective effects of Hochuekkito on sperm was suggested. Although normal sperm with ASA was used in this report, since the sperm of infertile patients are said to be more fragile, this results imply that direct protective effect is one of the mechanism of Hochuekkito for male infertility.

Adult↗
PubMed1998

[Is medical linac suitable for high-precision stereotactic irradiation?: investigations in geometrical accuracies of gantry and couch].

Linac-based radiosurgery has many advantages over the gamma knife, including low initial cost and no need of source replacement. On the other hand, most of the medical linacs currently in use were not originally designed to be applied for radiosurgery, and, therefore, careful quality assurance programs are required. In the gantry-head of a linac, a small CCD video camera is mounted in a position optically identical to that of the x-ray source. The video signal from the camera was digitalized to be evaluated for geometrical errors. A metal ball fixed to the stereotactic base frame via XYZ-sliding rods was used as a simulated target. Displacements of the target from the isocenter were measured during rotation of the gantry. Displacements in the gantry-rotation plane were satisfactorily small, while those perpendicular to it were maximal at gantry position angles of 0 degree and 180 degrees. This error night be caused by gravitational vending of the heavy gantry head. Although other major errors of the linac were within one millimeter, the center of coach rotation around the isocenter did not coincide with the center of gantry rotation, probably owing to gravitational vending. Special care should be taken when very small collimators are employed.

Quality Control↗
PubMed1998

[Surgical results and long-term outcome after mitral and/or tricuspid valve re-replacement].

Based on the STS/AATS guidelines of 1996, we compared the long-term results after mitral (Re-MVR) and/or tricuspid valve re-replacement (Re-TVR) in a total 324 patients (Re-MVT 299.Re-MVT+TVR 19, and Re-TVR 6 patients) with those after initial valve replacement in 763 patients (MVR 741, MVR+TVR 6 and TVR 16 patients). The actuarial survival (AS), reoperation-free (RF), thromboembolism-free (TF), and freedom from all valve-related events (EF) rates at the 15th postoperative year were 69.3%, 82.4% 86.6%, and 48.9% after Re-MVR and 87.2%, 92.2%, 83.9%, and 61.4% after initial MVR, respectively. The only significant difference between the two MVR groups occurred in the RF proportion. Similarly, the incidence of valve-related events after Re-MVR+TVR or Re-TVR was the same as that after the initial operation for the respective valve lesions. These long-term results suggest that valve re-replacement for mitral and/or tricuspid valve lesions should be encouraged to the same extent as the initial operation.

Adolescent↗
PubMed1998

[Necrosis of the hepatocellular carcinoma nodule can aggravate metastasis].

Since the stroma of hepatocellular carcinoma is composed of sinusoid-like structures, cancer cells are readily released from the primary tumor with possible injurious consequences. A 63-year-old woman with hepatocellular carcinoma underwent percutaneous ethanol injection therapy. During this treatment, tumor thrombus developed in the right hepatic vein. Partial hepatic resection was performed. Six months later, multiple nodules appeared in the lung fields. Partial necrosis may have allowed the release of cancer cells from the primary tumor. Perioperative therapy should have an effect on intrahepatic micrometastases, because removal of the main tumor can be done surgically.

Carcinoma, Hepatocellular↗
PubMed1998

Effect of nitric oxide-releasing aspirin derivative on gastric functional and ulcerogenic responses in rats: comparison with plain aspirin.

The effects of a nitric oxide (NO)-releasing derivative of aspirin, NCX-4016, on gastric functional and ulcerogenic responses in rat stomachs were examined in comparison with those of aspirin. Topical application of aspirin (80 mM) to the stomach markedly decreased transmucosal potential difference and slightly increased luminal pH (acid back-diffusion) with minimal effect on mucosal blood flow, whereas NCX-4016 caused a marked increase in mucosal blood flow with no effect on potential difference and pH. Aspirin itself was ulcerogenic, causing damage in the mucosa when administered p.o., and it markedly potentiated gastric ulcerogenic response to hypothermic stress (28 degrees C-30 degrees C) with no effect on acid secretion when given s.c. NCX-4016, however, was not ulcerogenic by itself, did not modify the ulcerogenic response to stress and even showed a dose-dependent protection against HCl/ethanol-induced gastric lesions. When NCX-4016 was given intragastrically to pylorus-ligated rats, a large amount of NO was detected in both gastric contents and serum. NCX-4016 administered either p.o. or s.c. produced an equipotent inhibition of mucosal PGE2 generation in the stomach, as compared with aspirin. In addition, both aspirin and NCX-4016 suppressed carrageenan-induced rat paw edema. These results suggest that, unlike aspirin, the NO-releasing derivative of aspirin NCX-4016 neither had a topical irritating action on the stomach nor exerted a worsening effect on gastric ulcerogenic response to stress, but rather provided gastric protection against ethanol, despite inhibiting cyclo-oxygenase activity and showing anti-inflammatory action much as aspirin does. NCX-4016, probably by releasing NO, exerted protective effects that counteracted the potential damaging effects of cyclo-oxygenase inhibition.

Animals↗
PubMed1998

[Radiobiological considerations for stereotactic irradiation].

Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a single high dose) was initially developed by Leksell for non-malignant brain lesions, but there has been increasing interest in using it to treat small primary brain tumors or metastases. In more recent years, stereotactic radiotherapy (SRT: fractionated STI) has been developed, but radiobiological factors have not been sufficiently evaluated in relation to these techniques. Larson classified potential STI targets into four categories according to whether the target tissue is early- or late-responding and whether it is embedded within or only surrounded by normal tissue. We have actually calculated biologically effective doses for these categories to determine the indications for SRS and SRT, and to be able to choose suitable SRT schedules. Based on our calculations, theoretically SRS would be recommended for AVMs and benign tumors having distinct margins separating them from surrounding normal tissue and SRT would be recommended for low or high grade astrocytomas without clearly defined boundaries and metastasis. Recommended SRT schedules would be 49 Gy/7 fractions, 52 Gy/8 fractions or 54.9 Gy/9 fractions completed within 2 weeks. However, clinically, these indications and SRT schedules should be modified according to the many other factors involved in individual cases, such as tumor size, presence of tumor necrosis, the patient's general condition, prognosis, and so on.

Brain↗
PubMed1998

[Intrahepatic arterial infusion chemotherapy with angiotensin II for liver metastasis from gastric cancer].

The theoretical purpose of induced hypertensive chemotherapy used together with injection of Angiotensin II is to increase the delivery of anticancer drug to the target tumor tissue by increasing blood flow in the tumor. Angiotensin II (50 micrograms) was dissolved in 50 ml of normal saline, and given through a peripheral vein by a microinfusion pump. When systolic pressure rose to about 140 to 150 mmHg, mitomycin C (10 to 20 mg/body) was given for 10 minutes via implanted port, whose tip was located in hepatic artery, followed by continuous infusion of 5-FU at 250 mg/day for 5 days. Response could be measured in 7 of all 10 cases (70.0%), CR was found in 4 and PR in 3. As for complications, one case of pseudo-aneurysm and one case of bile duct necrosis owing to drug toxicity were observed. Bone metastases or carcinomatous peritonitis occurred after a few months in two CR cases. We concluded that this mode of chemotherapy was a useful measure for the treatment of liver metastases from gastric cancer.

Aged↗
PubMed1998

[Schedule of stereotactic radiotherapy: a study considering the factors of repair and cell proliferation].

Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a single high dose) was initially developed by Leksell for non-malignant brain lesions, but there has been increasing interest in using it to treat small primary brain tumors or metastases. Recently, stereotactic radiotherapy (SRT: fractionated STI) has been recommended on the basis of radiobiological considerations for tumors in which both normal glial cells and tumor cells reside within the tumor margin. Strangely, the factors 'repair' and 'cell proliferation' have been neglected in the radiobiological evaluations of STI reported so far, mainly because of the complexity of the calculations. 'Half-time repair' which is the key value in the 'repair' factor may be larger for nervous tissue than for many other normal tissues because nerve cells have decreased ability to recover from damage. 'Cell proliferation' should be an important factor when the total radiation period is extended by applying SRT. In this study, we created models based on estimated 'half-time repair' and 'cell doubling time' and attempted to determine optimal SRT schedules. When repair and cell proliferation factors are also taken into consideration, the recommended SRT schedules would be 7 Gy x 7 fractions every other day for malignant tumors and 3.5 Gy x 12 fractions every other day for benign tumors. However, clinically, these schedules should be modified according to factors in individual cases, e. g., tumor size, presence of tumor necrosis, the patient's general condition, prognosis, and so on.

Brain↗
PubMed1997

The human beta globin locus introduced by YAC transfer exhibits a specific and reproducible pattern of developmental regulation in transgenic mice.

The human beta globin locus spans an 80-kb chromosomal region encompassing both the five expressed globin genes and the cis-acting elements that direct their stage-specific expression during ontogeny. Sequences proximal to the genes and in the locus control region, 60 kb upstream of the adult beta globin gene, are required for developmental regulation. Transgenic studies have shown that altering the structural organization of the locus disrupts the normal pattern of globin gene regulation. Procedures for introducing yeast artificial chromosomes (YACs) containing large genetic loci now make it possible to define the sequences required for stage-restricted gene expression in constructs that preserve the integrity of the beta globin locus. We demonstrate that independent YAC transgenic lines exhibit remarkably similar patterns of globin gene expression during development. The switch from gamma to beta globin predominant expression occurs between day 11.5 and 12.5 of gestation, with no more than twofold differences in human beta globin mRNA levels between lines. Human beta globin mRNA levels were twofold to fourfold lower than that of mouse betamaj, revealing potentially significant differences in the regulatory sequences of the two loci. These findings provide an important basis for studying regulatory elements within the beta globin locus.

Adult↗
PubMed1997

c-Jun/AP-1, but not NF-kappa B, is a mediator for oxidant-initiated apoptosis in glomerular mesangial cells.

Oxidant stress is a trigger of cell death in various cell types. Hydrogen peroxide (H2O2) induced mesangial cell death with nuclear condensation and DNA fragmentation typical of apoptosis. To explore molecular mechanisms involved in this process, redox-sensitive transacting molecules, activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B), have been brought into focus. Northern blot analysis and transient transfection assays using reporter plasmids showed that H2O2 activated both AP-1 and NF-kappa B. Downregulation of c-Jun/AP-1 using a transdominant negative mutant of c-jun, an antisense c-jun, or a pharmacologic inhibitor curcumin inhibited the H2O2-initiated apoptosis. In contrast, inhibition of the NF-kappa B activation using a transdominant negative mutant of the p50 NF-kappa B subunit did not affect the H2O2-triggered cellular death. These data elucidated that c-Jun/AP-1, but not NF-kappa B, is involved in the oxidant-initiated cell death program in glomerular mesangial cells.

Animals↗
PubMed1997

Cloning and expression of the dog mast cell alpha-chymase gene.

Chymases are chymotrypsin-like serine proteinases secreted by mast cells. Alpha- and beta-chymases differ in structure, function, and mast cell subset- and species-specific expression. Seeking genetic regulatory elements shared by alpha-chymases, we sequenced the dog alpha-gene. Extensive homology was found in intronic and flanking sequences of the dog, human, and mouse alpha-chymase genes, but little in corresponding beta-chymase sequences. Repetitive elements probably derived from retroposons are unique features of the dog flank. DNA blots suggest that the dog alpha-gene, like its human counterpart, may be the genome's sole chymase, unlike in rodents, in which beta-chymases predominate. Nuclear runoff studies predict that transcriptional mechanisms explain differences in steady state chymase and tryptase mRNA levels between mastocytoma and non-mast cells. In dog BR mastocytoma cells incubated with phorbol ester, high steady state levels of alpha-chymase mRNA drop dramatically with little change in tryptase mRNA, whereas dexamethasone decreases expression of both mRNAs. Portions of the dog or human gene 5' flank transfected into BR cells drive expression of a reporter gene and define regions with active promoters. Thus, BR cells express high levels of alpha-chymase mRNA regulated independently of tryptase and support transcription using dog or human promoters. These studies reinforce the alphabeta-chymase dichotomy and suggest the utility of BR cells in probing regulation of alpha-chymase expression.

Animals↗
PubMed1997

Cytokines promote glomerular mesangial cell survival in vitro by stimulus-dependent inhibition of apoptosis.

Resolution of glomerular inflammation requires the removal of proliferating resident glomerular mesangial cells, but excessive loss of glomerular cells is a feature of postinflammatory scarring. Because apoptosis regulates mesangial cell number in glomerular inflammation, we have studied the exogenous control of apoptosis triggered in cultured mesangial cells by stimuli likely to be important in vivo. Apoptosis could be induced by serum deprivation to model decreased availability of survival factors, by etoposide as an example of DNA-damaging agents, by ligation of mesangial cell Fas, and by protein synthesis inhibition by cycloheximide. Insulin-like growth factor I (IGF-I), IGF-II, and basic fibroblast growth factor were each able to suppress apoptosis induced by serum deprivation, whereas TGF-beta 1, epidermal growth factor, and platelet-derived growth factor had no effect. IGF-I and IGF-II (but not basic fibroblast growth factor) were also able to protect cells from apoptosis induced by etoposide or cycloheximide. However, Fas-mediated apoptosis was resistant to suppression by all three cytokines. None of the cytokines tested caused a change in the levels of expression of Bcl-2, Bax, Bcl-x, or Bak proteins. The survival-promoting properties of serum-free medium conditioned by mesangial cells was abrogated by neutralizing IGF-I Ab. These experiments are the first to define cytokines that inhibit apoptosis and thereby promote survival of mesangial cells, and the data indicate a paracrine survival signaling role for IGF-I. Finally, the data show that Fas ligation can override cytokine survival signaling, emphasizing a candidate role for this molecule in the undesirable apoptotic loss of mesangial cells during the progression of glomerular scarring.

Animals↗
PubMed1997

Creation of an In vivo cytosensor using engineered mesangial cells. Automatic sensing of glomerular inflammation controls transgene activity.

Automatic control over exogenous gene expression in response to the activity of disease is a crucial hurdle for gene transfer-based therapies. Towards achieving this goal, we created a "cytosensor" that perceives local inflammatory states and subsequently regulates foreign gene expression. alpha-Smooth muscle actin is known to be expressed in glomerular mesangial cells exclusively in pathologic situations. CArG box element, the crucial regulatory sequence of the alpha-smooth muscle actin promoter, was used as a sensor for glomerular inflammation. Rat mesangial cells were stably transfected with an expression plasmid that introduces a beta-galactosidase gene under the control of CArG box elements. In vitro, the established cells expressed beta-galactosidase exclusively after stimulation with serum. To examine whether the cells are able to automatically control transgene activity in vivo, serum-stimulated or unstimulated cells were transferred into normal rat glomeruli or glomeruli subjected to anti-Thy 1 glomerulonephritis. When stimulated cells were transferred into the normal glomeruli, beta-galactosidase expression was switched off in vivo within 3 d. In contrast, when unstimulated cells were transferred into the nephritic glomeruli, transgene expression was substantially induced. These data indicate the feasibility of using the CArG box element as a molecular sensor for glomerular injury. In the context of advanced forms of gene therapy, this approach provides a novel concept for automatic regulation of local transgene expression where the transgene is required to be activated during inflammation and deactivated when the inflammation has subsided.

Actins↗